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Bibliography on: Mitochondrial Evolution

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ESP: PubMed Auto Bibliography 03 Dec 2024 at 01:56 Created: 

Mitochondrial Evolution

The endosymbiotic hypothesis for the origin of mitochondria (and chloroplasts) suggests that mitochondria are descended from specialized bacteria (probably purple nonsulfur bacteria) that somehow survived endocytosis by another species of prokaryote or some other cell type, and became incorporated into the cytoplasm.

Created with PubMed® Query: ( mitochondria AND evolution NOT 26799652[PMID] NOT 33634751[PMID] NOT 38225003[PMID]) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2024-12-01

Zhao J, Liang ZL, Fang SL, et al (2024)

Phylogenomics of Paragymnopteris (Cheilanthoideae, Pteridaceae): Insights from plastome, mitochondrial, and nuclear datasets.

Molecular phylogenetics and evolution pii:S1055-7903(24)00245-8 [Epub ahead of print].

Previous studies have shown that at least six genera of the Cheilanthoideae, a subfamily of the fern family Pteridaceae, may not be monophyletic. In these non-monophyletic genera, the Old-World genus Paragymnopteris including approximately five species have long been controversial. In this study, with an extensive taxon sampling of Paragymnopteris, we assembled 19 complete plastomes of all recognized Paragymnopteris species, plastomes of Pellaea (3 species) and Argyrochosma (1 species), as well as transcriptomes from Paragymnopteris (6 species) and Argyrochosma (1 species). We conducted a comprehensive and systematic phylogenomic analysis focusing on the contentious relationships among the genus of Paragymnopteris through 9 plastid makers, the plastomes, mitochondria, nuclear ribosomal cistron genomes, and single-copy nuclear genes. Moreover, we further combined distribution, ploidy, and morphological features to investigate the evolution of Paragymnopteris. The backbone of Paragymnopteris was resolved consistently in the nuclear and plastid phylogenies. Our major results include: (1) Paragymnopteris is not monophyletic including two fully supported clades; (2) confirming that Paragymnopteris delavayi var. intermedia is a close relative of P. delavayi instead of P. marantae var. marantae; (3) the chromosome base number may not be a stable trait which has previously been used as an important character to divide Paragymnopteris into two groups; and (4) gene flow or introgression might be the main reason for the gene trees conflict of Paragymnopteris, but both gene flow and ILS might simultaneously and/or cumulatively act on the conflict of core pellaeids. The robust phylogeny of Paragymnopteris presented here will help us for the future studies of the arid to semi-arid ferns of Cheilanthoideae at the evolutionary, physiological, developmental, and omics-based levels.

RevDate: 2024-11-30
CmpDate: 2024-11-30

Xin C, Wang J, Chi J, et al (2025)

Intragenic cytosine methylation modification regulates the response of SUCLα1 to lower temperature in Solanaceae.

Plant science : an international journal of experimental plant biology, 350:112320.

The tricarboxylic acid cycle (TCAC) is a fundamental metabolic process governing matter and energy in plant cells, playing an indispensable role. However, its involvement in responding to low temperature stress in potato remains poorly understood. Previous studies have identified succinyl-CoA ligase (SUCL), which catalyzes the phosphorylation of TCAC substrates, as a gene associated with lower temperatures. Nevertheless, its function in potato's response to lower temperatures remains unclear. Phylogenetic analysis has revealed that Solanum tuberosum possesses α and β subunits of SUCL, which cluster with those of Solanum lycopersicum, Nicotiana tabacum and Nicotiana benthamiana. Further investigation has shown that StSUCLα1 is predominantly located within mitochondria. Low temperatures induce methylation modification alterations at 11 intragenic cytosine sites and lead to changes in StSUCLα1 expression levels. Correlation analysis suggests that alterations in intragenic cytosine methylation sites of SUCLα1 may be associated with MET1. Knocking down NbSUCLα1, the homologous gene of StSUCLα1 in N. benthamiana, results in increased susceptibility to low temperature stress in plants. In summary, we have confirmed that SUCLα1 is a key gene modulated by intragenic cytosine methylation in response to lower temperatures, providing a novel target for genetic breeding aimed at enhancing potato tolerance to low temperature stress.

RevDate: 2024-12-01
CmpDate: 2024-12-01

Forbes K, Barrera M, Nielsen-Roine K, et al (2024)

Stabilizing selection and mitochondrial heteroplasmy in the Canada lynx (Lynx canadensis).

Genome, 67(12):493-502.

Mitochondrial DNA is commonly used in population genetic studies to investigate spatial structure, intraspecific variation, and phylogenetic relationships. The control region is the most rapidly evolving and largest non-coding region, but its analysis can be complicated by heteroplasmic signals of genome duplication in many mammals, including felids. Here, we describe the presence of heteroplasmy in the control region of Canada lynx (Lynx canadensis) through intra-individual sequence variation. Our results demonstrate multiple haplotypes of varying length in each lynx, resulting from different copy numbers of the repetitive sequence RS-2 and suggest possible heteroplasmic single nucleotide polymorphisms in both repetitive sequences RS-2 and RS-3. Intra-individual variation was only observed in the repetitive sequences while inter-individual variation was detected in the flanking regions outside of the repetitive sequences, indicating that heteroplasmic mutations are restricted to these repeat regions. Although each lynx displayed multiple haplotypes of varying length, we found the most common variant contained three complete copies of the RS-2 repeat unit, suggesting copy number is regulated by stabilizing selection. While genome duplication offers potential for increased diversity, heteroplasmy may lead to a selective advantage or detriment in the face of mitochondrial function and disease, which could have significant implications for wildlife populations experiencing decline (e.g., bottlenecks) as a result of habitat modification or climate change.

RevDate: 2024-11-28

Nolbrant S, Wallace JL, Ding J, et al (2024)

Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.

bioRxiv : the preprint server for biology pii:2024.11.14.623592.

The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release. We identify human-specific gene expression changes related to axonal transport of mitochondria and reactive oxygen species buffering and candidate cis- and trans -regulatory mechanisms underlying gene expression divergence. Our findings are consistent with a model of evolved neuroprotection in response to tradeoffs related to brain expansion and could contribute to the discovery of therapeutic targets and strategies for treating disorders involving the dopaminergic system.

RevDate: 2024-11-28
CmpDate: 2024-11-28

Liao R, Yao J, Zhang Y, et al (2024)

MYB transcription factors in Peucedanum Praeruptorum Dunn: the diverse roles of the R2R3-MYB subfamily in mediating coumarin biosynthesis.

BMC plant biology, 24(1):1135.

BACKGROUND: The MYB superfamily (v-myb avian myeloblastosis viral oncogene homolog) plays a role in plant growth and development, environmental stress defense, and synthesis of secondary metabolites. Little is known about the regulatory function of MYB genes in Peucedanum praeruptorum Dunn, although many MYB family members, especially R2R3-MYB genes, have been extensively studied in model plants.

RESULTS: A total of 157 R2R3-MYB transcription factors from P. praeruptorum were identified using bioinformatics analysis. Comprehensive analyses including chromosome location, microsynteny, gene structure, conserved motif, phylogenetic tree, and conserved domain were further performed. The length of the 157 transcription factors ranged from 120 to 1,688 amino acids (molecular weight between 14.21 and 182.69 kDa). All proteins were hydrophilic. Subcellular localization predictions showed that 155 PpMYB proteins were localized in the nucleus, with PpMYB12 and PpMYB157 localized in the chloroplasts and mitochondria, respectively. Ten conserved motifs were identified in the PpMYBs, all of which contained typical MYB domains. Transcriptome analysis identified 47,902 unigenes. Kyoto Encyclopedia of Genes and Genomes analysis revealed 136 pathways, of which 524 genes were associated with the phenylpropanoid pathway. Differential expressed genes (DEGs) before and after bolting showed that 11 genes were enriched in the phenylpropanoid pathway. Moreover, the expression patterns of transcription genes were further verified by qRT-PCR. With high-performance liquid chromatography (HPLC), 8 coumarins were quantified from the root, stem, and leaf tissue samples of P. praeruptorum at different stages. Praeruptorin A was found in both roots and leaves before bolting, whereas praeruptorin B was mainly concentrated in the roots, and the content of both decreased in the roots and stems after bolting. Praeruptorin E content was highest in the leaves and increased with plant growth. The correlation analysis between transcription factors and coumarin content showed that the expression patterns of PpMYB3 and PpMYB103 in roots align with the accumulation trends of praeruptorin A, praeruptorin B, praeruptorin E, scopoletin, and isoscopoletin, which declined in content after bolting, suggesting that these genes may positively regulate the biosynthesis of coumarins. Eleven distinct metabolites and 48 DEGs were identified. Correlation analysis revealed that the expression of all DEGs were significantly related to the accumulation of coumarin metabolites, indicating that these genes are involved in the regulation of coumarin biosynthesis.

CONCLUSIONS: R2R3-MYB transcription factors may be involved in the synthesis of coumarin. Our findings provide basic data and a rationale for future an in-depth studies on the role of R2R3-MYB transcription factors in the growth and regulation of coumarin synthesis.

RevDate: 2024-11-27

Haro R, Walunjkar N, Jorapur S, et al (2024)

Long-read DNA sequencing reveals the organization of the mitochondrial genome in the early-branching dinoflagellate Oxyrrhis marina.

Protist, 175(6):126071 pii:S1434-4610(24)00063-4 [Epub ahead of print].

The mitochondrial genomes of dinoflagellate protists are remarkable for their highly fragmented and heterogeneous organization. Early attempts to determine their structure without 'next-generation' DNA sequencing failed to recover a defined genome. Still, it coincided in showing that the proteins coding genes, three in total, and parts of the ribosomal RNA genes were spread across a diffuse assortment of small linear fragments. In contrast, a recent study employed Illumina sequencing to assemble a 326 kbp long single-molecule, circular mitochondrial genome in the symbiotic dinoflagellate Breviolum minutum. Here, we used a combination of short- and long-read massively-parallel DNA sequencing to analyze further the mitochondrial DNA of the early-branching dinoflagellate Oxyrrhis marina. We found that the mitochondrial genome of O. marina consists of 3 linear chromosomes sized 15.9, 33.8 and 40.6 kbp for a total of 90.3 kbp. It contains the cox1, cox3 and cob genes, the same three proteins encoded in the mitochondrion of all myzozoans (Apicomplexa and Dinophyceae), some fragments of ribosomal RNA genes as well as many non-functional gene fragments and extensive noncoding DNA. Our analysis unveiled segments syntenic patterns and rearrangements encompassing coding and non-coding regions, suggesting that recombination is a pervasive process driving the evolution of these genomes.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Wang X, Wang Z, Yang F, et al (2024)

Assembly, Annotation, and Comparative Analysis of Mitochondrial Genomes in Trichoderma.

International journal of molecular sciences, 25(22): pii:ijms252212140.

Trichoderma is a widely studied ascomycete fungal genus, including more than 400 species. However, genetic information on Trichoderma is limited, with most species reporting only DNA barcodes. Mitochondria possess their own distinct DNA that plays a pivotal role in molecular function and evolution. Here, we report 42 novel mitochondrial genomes (mitogenomes) combined with 18 published mitogenomes of Trichoderma. These circular mitogenomes exhibit sizes of 26,276-94,608 bp, typically comprising 15 core protein-coding genes (PCGs), 2 rRNAs, and 16-30 tRNAs; however, the number of endonucleases and hypothetical proteins encoded in the introns of PCGs increases with genome size enlargement. According to the result of phylogenetic analysis of the whole mitogenome, these strains diverged into six distinct evolutionary branches, supported by the phylogeny based on 2830 single-copy nuclear genes. Comparative analysis revealed that dynamic Trichoderma mitogenomes exhibited variations in genome size, gene number, GC content, tRNA copy, and intron across different branches. We identified three mutation hotspots near the regions encoding nad3, cox2, and nad5 that caused major changes in the mitogenomes. Evolutionary analysis revealed that atp9, cob, nad4L, nad5, and rps3 have been influenced by positive selection during evolution. This study provides a valuable resource for exploring the important roles of the genetic and evolutionary dynamics of Trichoderma mitogenome in the adaptive evolution of biocontrol fungi.

RevDate: 2024-11-27
CmpDate: 2024-11-27

Wang H, Charagh S, Dong N, et al (2024)

Genome-Wide Analysis of Heat Shock Protein Family and Identification of Their Functions in Rice Quality and Yield.

International journal of molecular sciences, 25(22): pii:ijms252211931.

Heat shock proteins (Hsps), acting as molecular chaperones, play a pivotal role in plant responses to environmental stress. In this study, we found a total of 192 genes encoding Hsps, which are distributed across all 12 chromosomes, with higher concentrations on chromosomes 1, 2, 3, and 5. These Hsps can be divided into six subfamilies (sHsp, Hsp40, Hsp60, Hsp70, Hsp90, and Hsp100) based on molecular weight and homology. Expression pattern data indicated that these Hsp genes can be categorized into three groups: generally high expression in almost all tissues, high tissue-specific expression, and low expression in all tissues. Further analysis of 15 representative genes found that the expression of 14 Hsp genes was upregulated by high temperatures. Subcellular localization analysis revealed seven proteins localized to the endoplasmic reticulum, while others localized to the mitochondria, chloroplasts, and nucleus. We successfully obtained the knockout mutants of above 15 Hsps by the CRISPR/Cas9 gene editing system. Under natural high-temperature conditions, the mutants of eight Hsps showed reduced yield mainly due to the seed setting rate or grain weight. Moreover, the rice quality of most of these mutants also changed, including increased grain chalkiness, decreased amylose content, and elevated total protein content, and the expressions of starch metabolism-related genes in the endosperm of these mutants were disturbed compared to the wild type under natural high-temperature conditions. In conclusion, our study provided new insights into the HSP gene family and found that it plays an important role in the formation of rice quality and yield.

RevDate: 2024-11-24
CmpDate: 2024-11-24

Wang Y, Chen F, Chen Y, et al (2024)

Identification and analysis of drought-responsive F-box genes in upland rice and involvement of OsFBX148 in ABA response and ROS accumulation.

BMC plant biology, 24(1):1120.

BACKGROUND: Upland rice varieties exhibit significant genetic diversity and broad environmental adaptability, making them ideal candidates for identifying consistently expressed stress-responsive genes. F-box proteins typically function as part of the SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes to precisely regulate gene expression and protein level, playing essential roles in the modulation of abiotic stress responses. Therefore, utilizing upland rice varieties for screening stress-responsive F-box genes is a highly advantageous approach.

RESULTS: Through mRNA-seq analysis in the Brazilian upland rice (cv. IAPAR9), the research identified 29 drought-responsive F-box genes. Gene distribution and duplication analysis revealed these genes are distributed on 11 of the 12 chromosomes and 10 collinear gene pairs were identified on different chromosomes. 13 cis-elements or binding sites were identified in the promoters of the 29 drought-responsive F-box genes by analysis. Protein domain, stability and subcellular localization analysis results suggest that these F-box proteins possess F-box domain and several other domains, and they are mostly unstable proteins with subcellular localization in cytoplasm, nucleus, chloroplasts, mitochondria and endoplasmic reticulum. Most of drought-responsive F-box genes exhibited expression in various tissues such as root, stem, leaf, leaf sheath and panicle except for OsFBO10 and OsFBX283. These genes exhibited various responses to abiotic stresses such as osmotic, cold, heat, and salt stresses, along with ABA treatment. Importantly, a frame-shift mutation in OsFBX148 was created in the ZH11 variety, leading to altered ABA signal transduction and ROS accumulation. The study further elucidated the interaction of OsFBX148 with SKP1 family proteins OSK4/7/17 to form the SCF complex, dependent on the F-box domain.

CONCLUSIONS: The research identified and analyzed 29 drought-responsive F-box genes in upland rice and provides valuable insights into the role of OsFBX148 in ABA and ROS responses. It establishes a basis for future exploration of F-box genes in improving resistance to abiotic stresses, especially drought.

RevDate: 2024-11-21

Anikin M, Henry MF, Hodorova V, et al (2024)

Mitochondrial mRNA and the Small Subunit rRNA in Budding Yeasts Undergo 3'-End Processing at Conserved Species-specific Elements.

RNA (New York, N.Y.) pii:rna.080254.124 [Epub ahead of print].

Respiration in eukaryotes depends on mitochondrial protein synthesis, which is performed by organelle-specific ribosomes translating organelle-encoded mRNAs. Although RNA maturation and stability are central events controlling mitochondrial gene expression, many of the molecular details in this pathway remain elusive. These include cis- and trans-regulatory factors that generate and protect the 3' ends. Here, we mapped the 3' ends of mitochondrial mRNAs of yeasts classified into multiple families of the subphylum Saccharomycotina. We found that the processing of mitochondrial 15S rRNA and mRNAs involves species-specific sequence elements, which we term 3'-end RNA processing elements (3'-RPEs). In Saccharomyces cerevisiae, the 3'-RPE has long been recognized as a conserved dodecamer sequence, which recent studies have shown to specifically interact with the nuclear genome-encoded pentatricopeptide repeat protein Rmd9. We also demonstrate that, analogous to Rmd9 in Saccharomyces cerevisiae, two Rmd9 orthologs from the Debaryomycetaceae family interact with their respective 3'-RPEs found in mRNAs and 15S rRNA. Thus, Rmd9-dependent processing of mitochondrial RNA precursors is a common mechanism among the families of the Saccharomycotina subphylum. This represents an example of mitochondrial-nuclear co-evolution. Surprisingly, we observed that 3'-RPEs often occur upstream of stop codons in complex I subunit mRNAs from yeasts of the CUG-Ser1 clade. We examined two of these mature mRNAs and found that their stop codons are indeed removed. Thus, translation of these transcripts would require a novel termination mechanism. Our findings establish Rmd9 as a key evolutionarily conserved factor in both mitochondrial mRNA metabolism and mitoribosome biogenesis in a variety of yeasts.

RevDate: 2024-11-20

Jinesh GG, Smallin MT, Mtchedlidze N, et al (2024)

C19MC drives nucleolar invasion of mitochondria and meiotic nuclear division in human cancers.

iScience, 27(11):111132.

The chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated state of placental trophoblasts. However, the relationship of C19MC to multinucleation is unknown. Here we show that C19MC is coexpressed in multiple cancer type subsets with meiosis-related genes. We discovered a novel meiosis-III that exhibits simultaneous progression of meiotic nuclear division (MND) and cytokinesis. C19MC promotes meiotic bridged-chromosomes to block MND and cytokinesis to generate multinucleated cells. MND starts with the invagination of nuclear membrane to form nucle(ol)ar invasive cytoplasm (NiC), mitochondria and protein cargoes. Aurora-B regulates the efflux of cargos from NiC, whereas C19MC, CDK1, and autophagy promote cargo influx to inflate NiC size for MND progression. Using CRISPR human genetic engineering we demonstrate that the C19MC expression is required for NiC-driven MND and multinucleation. This discovery has impacts on cancer-pathogen interactions, immunotherapy, vertical transmission of viruses, antiviral research and SpCas9-CRISPR therapeutics.

RevDate: 2024-11-20
CmpDate: 2024-11-20

Wang Z, Wang R, Sang Y, et al (2024)

Comparative analysis of mitochondrial genomes of invasive weed Mikania micrantha and its indigenous congener Mikania cordata.

International journal of biological macromolecules, 281(Pt 1):136357.

Mikania micrantha and Mikania cordata are two distinct species in China. The former is notorious as one of the top 100 worst invasive species, whereas the latter is an indigenous species harmless to native plants or the environment. They form an ideal congener pair for comparative studies aimed at deeply understanding the invasion mechanisms of the exotic weed. In this study, we have assembled and annotated the mitogenomes of both species using Illumina and PacBio sequencing data and compared their characteristic differences. The complete mitogenome of M. micrantha is a double-stranded DNA with a length of 336,564 bp, while the mitogenome of M. cordata exhibits a branching structure, consisting of two small circular molecules and six linear molecules, with a combined length totaling 335,444 bp. Compared to M. cordata, M. micrantha has less SSRs, tandem repeats, dispersed repeats, mitochondrial protein coding genes (PCGs). The two plants show similar codon usage patterns. This comparative study has revealed the structure and function of the mitogenomes of the two species and laid a solid foundation for investigating the effects of gene loss and duplication on the development of invasive traits in M. micrantha.

RevDate: 2024-11-19

Povelones ML, ML Ginger (2024)

Bric-à-brac, an 'umbilical cord' and trypanosome kinetoplast segregation.

Trends in parasitology pii:S1471-4922(24)00329-5 [Epub ahead of print].

Cadena et al. recently discovered a conserved trypanosomatid 'nabelschnur' protein TbNAB70 from a search through the protein localization resource TrypTag, providing new insight into kinetoplast origin and evolution.

RevDate: 2024-11-18

Kemph A, Kharel K, Tindell SJ, et al (2024)

Novel structure and composition of the unusually large germline determinant of the wasp Nasonia vitripennis.

bioRxiv : the preprint server for biology pii:2024.11.01.621563.

Specialized, maternally derived ribonucleoprotein (RNP) granules play an important role in specifying the primordial germ cells in many animal species. Typically, these germ granules are small (∼100 nm to a few microns in diameter) and numerous; in contrast, a single, extremely large granule called the oosome plays the role of germline determinant in the wasp Nasonia vitripennis. The organizational basis underlying the form and function of this unusually large membraneless RNP granule remains an open question. Here we use a combination of super-resolution and transmission electron microscopy to investigate the composition and morphology of the oosome. We show that the oosome has properties of a viscous liquid or elastic solid. The most prominent feature of the oosome is a branching mesh-like network of high abundance mRNAs that pervades the entire structure. Homologs of the core polar granule proteins Vasa and Oskar do not appear to nucleate this network, but rather are distributed adjacently as separate puncta. Low abundance RNAs appear to cluster in puncta that similarly do not overlap with the protein puncta. Several membrane-bound organelles, including lipid droplets and rough ER-like vesicles, are incorporated within the oosome, whereas mitochondria are nearly entirely excluded. Our findings show that the remarkably large size of the oosome is reflected in a complex sub-granular organization and suggest that the oosome is a powerful model for probing interactions between membraneless and membrane-bound organelles, structural features that contribute to granule size, and the evolution of germ plasm in insects.

RevDate: 2024-11-18
CmpDate: 2024-11-18

Ozerova I, Fallmann J, Mörl M, et al (2024)

Aberrant Mitochondrial tRNA Genes Appear Frequently in Animal Evolution.

Genome biology and evolution, 16(11):.

Mitochondrial tRNAs have acquired a diverse portfolio of aberrant structures throughout metazoan evolution. With the availability of more than 12,500 mitogenome sequences, it is essential to compile a comprehensive overview of the pattern changes with regard to mitochondrial tRNA repertoire and structural variations. This, of course, requires reanalysis of the sequence data of more than 250,000 mitochondrial tRNAs with a uniform workflow. Here, we report our results on the complete reannotation of all mitogenomes available in the RefSeq database by September 2022 using mitos2. Based on the individual cases of mitochondrial tRNA variants reported throughout the literature, our data pinpoint the respective hotspots of change, i.e. Acanthocephala (Lophotrochozoa), Nematoda, Acariformes, and Araneae (Arthropoda). Less dramatic deviations of mitochondrial tRNAs from the norm are observed throughout many other clades. Loss of arms in animal mitochondrial tRNA clearly is a phenomenon that occurred independently many times, not limited to a small number of specific clades. The summary data here provide a starting point for systematic investigations into the detailed evolutionary processes of structural reduction and loss of mitochondrial tRNAs as well as a resource for further improvements of annotation workflows for mitochondrial tRNA annotation.

RevDate: 2024-11-15

Jacobs HT, Rustin P, Bénit P, et al (2024)

Mitochondria: great balls of fire.

The FEBS journal [Epub ahead of print].

Recent experimental studies indicate that mitochondria in mammalian cells are maintained at temperatures of at least 50 °C. While acknowledging the limitations of current experimental methods and their interpretation, we here consider the ramifications of this finding for cellular functions and for evolution. We consider whether mitochondria as heat-producing organelles had a role in the origin of eukaryotes and in the emergence of homeotherms. The homeostatic responses of mitochondrial temperature to externally applied heat imply the existence of a molecular heat-sensing system in mitochondria. While current findings indicate high temperatures for the innermost compartments of mitochondria, those of the mitochondrial surface and of the immediately surrounding cytosol remain to be determined. We ask whether some aspects of mitochondrial dynamics and motility could reflect changes in the supply and demand for mitochondrial heat, and whether mitochondrial heat production could be a factor in diseases and immunity.

RevDate: 2024-11-15

Dondi A, Borgsmüller N, Ferreira PF, et al (2024)

De novo detection of somatic variants in high-quality long-read single-cell RNA sequencing data.

bioRxiv : the preprint server for biology pii:2024.03.06.583775.

In cancer, genetic and transcriptomic variations generate clonal heterogeneity, leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential to detect genetic and transcriptomic variations simultaneously. Here, we present LongSom, a computational workflow leveraging high-quality LR scRNA-seq data to call de novo somatic single-nucleotide variants (SNVs), including in mitochondria (mtSNVs), copy-number alterations (CNAs), and gene fusions, to reconstruct the tumor clonal heterogeneity. Before somatic variants calling, LongSom re-annotates marker gene based cell types using cell mutational profiles. LongSom distinguishes somatic SNVs from noise and germline polymorphisms by applying an extensive set of hard filters and statistical tests. Applying LongSom to human ovarian cancer samples, we detected clinically relevant somatic SNVs that were validated against matched DNA samples. Leveraging somatic SNVs and fusions, LongSom found subclones with different predicted treatment outcomes. In summary, LongSom enables de novo variant detection without the need for normal samples, facilitating the study of cancer evolution, clonal heterogeneity, and treatment resistance.

RevDate: 2024-11-14

Garcia LE, MV Sanchez-Puerta (2024)

Mitochondrial Splicing Efficiency Is Lower in Holoparasites Than in Free-Living Plants.

Plant & cell physiology pii:7900404 [Epub ahead of print].

Mitochondria play a crucial role in eukaryotic organisms, housing their own genome with genes vital for oxidative phosphorylation. Coordination between nuclear and mitochondrial genomes is pivotal for organelle gene expression. Splicing, editing and processing of mitochondrial transcripts are regulated by nuclear-encoded factors. Splicing efficiency (SEf) of the many group II introns present in plant mitochondrial genes is critical for mitochondrial function since a splicing defect or splicing deficiency can severely impact plant growth and development. This study investigates SEf in free-living and holoparasitic plants, focusing on 25 group II introns from 15 angiosperm species. Our comparative analyses reveal distinctive splicing patterns with holoparasites exhibiting significantly lower SEf, potentially linked to their unique evolutionary trajectory. Given the preponderance of horizontal gene transfer (HGT) in parasitic plants, we investigated the effect of HGT on SEf, such as the presence of foreign introns or foreign nuclear-encoded splicing factors. Contrary to expectations, the SEf reductions do not correlate with HGT events, suggesting that other factors are at play, such as the loss of photosynthesis or the transition to a holoparasitic lifestyle. The findings of this study broaden our understanding of the molecular evolution in parasitic plants and shed light on the multifaceted factors influencing organelle gene expression.

RevDate: 2024-11-13

van Westerhoven AC, Dijkstra J, Aznar Palop JL, et al (2024)

Frequent genetic exchanges revealed by a pan-mitogenome graph of a fungal plant pathogen.

mBio [Epub ahead of print].

Mitochondria are present in almost all eukaryotic lineages. The mitochondrial genomes (mitogenomes) evolve separately from nuclear genomes, and they can therefore provide relevant insights into the evolution of their host species. Fusarium oxysporum is a major fungal plant pathogen that is assumed to reproduce clonally. However, horizontal chromosome transfer between strains can occur through heterokaryon formation, and recently, signs of sexual recombination have been observed. Similarly, signs of recombination in F. oxysporum mitogenomes challenged the prevailing assumption of clonal reproduction in this species. Here, we construct, to our knowledge, the first fungal pan-mitogenome graph of nearly 500 F. oxysporum mitogenome assemblies to uncover the variation and evolution. In general, the gene order of fungal mitogenomes is not well conserved, yet the mitogenome of F. oxysporum and related species are highly colinear. We observed two strikingly contrasting regions in the F. oxysporum pan-mitogenome, comprising a highly conserved core mitogenome and a long variable region (6-16 kb in size), of which we identified three distinct types. The pan-mitogenome graph reveals that only five intron insertions occurred in the core mitogenome and that the long variable regions drive the difference between mitogenomes. Moreover, we observed that their evolution is neither concurrent with the core mitogenome nor with the nuclear genome. Our large-scale analysis of long variable regions uncovers frequent recombination between mitogenomes, even between strains that belong to different taxonomic clades. This challenges the common assumption of incompatibility between genetically diverse F. oxysporum strains and provides new insights into the evolution of this fungal species.IMPORTANCEInsights into plant pathogen evolution is essential for the understanding and management of disease. Fusarium oxysporum is a major fungal pathogen that can infect many economically important crops. Pathogenicity can be transferred between strains by the horizontal transfer of pathogenicity chromosomes. The fungus has been thought to evolve clonally, yet recent evidence suggests active sexual recombination between related isolates, which could at least partially explain the horizontal transfer of pathogenicity chromosomes. By constructing a pan-genome graph of nearly 500 mitochondrial genomes, we describe the genetic variation of mitochondria in unprecedented detail and demonstrate frequent mitochondrial recombination. Importantly, recombination can occur between genetically diverse isolates from distinct taxonomic clades and thus can shed light on genetic exchange between fungal strains.

RevDate: 2024-11-08
CmpDate: 2024-11-08

Speth DR, Zeller LM, Graf JS, et al (2024)

Genetic potential for aerobic respiration and denitrification in globally distributed respiratory endosymbionts.

Nature communications, 15(1):9682.

The endosymbiont Candidatus Azoamicus ciliaticola was proposed to generate ATP for its eukaryotic host, an anaerobic ciliate of the Plagiopylea class, fulfilling a function analogous to mitochondria in other eukaryotic cells. The discovery of this respiratory endosymbiosis has major implications for both evolutionary history and ecology of microbial eukaryotes. However, with only a single species described, knowledge of its environmental distribution and diversity is limited. Here we report four complete, circular metagenome assembled genomes (cMAGs) representing respiratory endosymbionts inhabiting groundwater in California, Ohio, and Germany. These cMAGs form two lineages comprising a monophyletic clade within the uncharacterized gammaproteobacterial order UBA6186, enabling evolutionary analysis of their key protein complexes. Strikingly, all four cMAGs encode a cytochrome cbb3 oxidase, which indicates that these endosymbionts have the capacity for aerobic respiration. Accordingly, we detect these respiratory endosymbionts in diverse habitats worldwide, thus further expanding the ecological scope of this respiratory symbiosis.

RevDate: 2024-11-07
CmpDate: 2024-11-08

Zhang K, Qu G, Zhang Y, et al (2024)

Assembly and comparative analysis of the first complete mitochondrial genome of Astragalus membranaceus (Fisch.) Bunge: an invaluable traditional Chinese medicine.

BMC plant biology, 24(1):1055.

BACKGROUND: Astragalus membranaceus (Fisch.) Bunge is one of the most well-known tonic herbs in traditional Chinese medicine, renowned for its remarkable medicinal value in various clinical contexts. The corresponding chloroplast (cp) and nuclear genomes have since been accordingly sequenced, providing valuable information for breeding and phylogeny studies. However, the mitochondrial genome (mitogenome) of A. membranaceus remains unexplored, which hinders comprehensively understanding the evolution of its genome.

RESULTS: For this study, we de novo assembled the mitogenome of A. membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P. K. Hsiao using a strategy integrating Illumina and Nanopore sequencing technology and subsequently performed comparative analysis with its close relatives. The mitogenome has a multi-chromosome structure, consisting of two circular chromosomes with a total length of 398,048 bp and an overall GC content of 45.3%. It encodes 54 annotated functional genes, comprising 33 protein-coding genes (PCGs), 18 tRNA genes, and 3 rRNA genes. An investigation of codon usage in the PCGs revealed an obvious preference for codons ending in A or U (T) bases, given their high frequency. RNA editing identified 500 sites in the coding regions of mt PCGs that exhibit a perfect conversion of the base C to U, a process that tends to lead to the conversion of hydrophilic amino acids into hydrophobic amino acids. From the mitogenome analysis, a total of 399 SSRs, 4 tandem repeats, and 77 dispersed repeats were found, indicating that A. membranaceus possesses fewer repeats compared to its close relatives with similarly sized mitogenomes. Selection pressure analysis indicated that most mt PCGs were purifying selection genes, while only five PCGs (ccmB, ccmFc, ccmFn, nad3, and nad9) were positive selection genes. Notably, positive selection emerged as a critical factor in the evolution of ccmB and nad9 in all the pairwise species comparisons, suggesting the extremely critical role of these genes in the evolution of A. membranaceus. Moreover, we inferred that 22 homologous fragments have been transferred from cp to mitochondria (mt), in which 5 cp-derived tRNA genes remain intact in the mitogenome. Further comparative analysis revealed that the syntenic region and mt gene organization are relatively conserved within the provided legumes. The comparison of gene content indicated that the gene composition of Fabaceae mitogenomes differed. Finally, the phylogenetic tree established from analysis is largely congruent with the taxonomic relationships of Fabaceae species and highlights the close relationship between Astragalus and Oxytropis.

CONCLUSIONS: We provide the first report of the assembled and annotated A. membranaceus mitogenome, which enriches the genetic resources available for the Astragalus genus and lays the foundation for comprehensive exploration of this invaluable medicinal plant.

RevDate: 2024-11-12
CmpDate: 2024-11-12

Erinjeri AP, Wang X, Williams R, et al (2024)

HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling.

Nature communications, 15(1):9797.

Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and mitochondria associated protein degradation, and that this is complemented by UBQL-1-dependent turnover of NPL-4.1. As a consequence, mitochondrial network dynamics are altered, leading to increased lifespan. Together, our data establish that HSF-1 mediates lifespan extension through mitochondrial network adaptations that occur in response to down-tuning of components associated with organellar protein degradation pathways.

RevDate: 2024-11-11

Salminen TS, Vesala L, Basikhina Y, et al (2024)

A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila.

PLoS genetics, 20(11):e1011476 pii:PGENETICS-D-24-00449 [Epub ahead of print].

The role of mitochondria in immunity is increasingly recognized, but it is unclear how variation in mitochondrial DNA (mtDNA) contributes to variable infection outcomes. To quantify the effect of mtDNA variation on humoral and cell-mediated innate immune responses, we utilized a panel of fruit fly Drosophila melanogaster cytoplasmic hybrids (cybrids), where unique mtDNAs (mitotypes) were introgressed into a controlled isogenic nuclear background. We observed substantial heterogeneity in infection outcomes within the cybrid panel upon bacterial, viral and parasitoid infections, driven by the mitotype. One of the mitotypes, mtKSA2 protected against bacterial, parasitoid, and to a lesser extent, viral infections. Enhanced survival was not a result of improved bacterial clearance, suggesting mtKSA2 confers increased disease tolerance. Transcriptome sequencing showed that the mtKSA2 mitotype had an upregulation of genes related to mitochondrial respiration and phagocytosis in uninfected flies. Upon infection, mtKSA2 flies exhibited infection type and duration specific transcriptomic changes. Furthermore, uninfected mtKSA2 larvae showed immune activation of hemocytes (immune cells), increased hemocyte numbers and ROS production, and enhanced encapsulation response against parasitoid wasp eggs and larvae. Our results show that mtDNA variation acts as an immunomodulatory factor in both humoral and cell-mediated innate immunity and that specific mitotypes can provide broad protection against infections.

RevDate: 2024-11-11

Gould SB, Magiera J, García García C, et al (2024)

Reliability of plastid and mitochondrial localisation prediction declines rapidly with the evolutionary distance to the training set increasing.

PLoS computational biology, 20(11):e1012575 pii:PCOMPBIOL-D-24-00460 [Epub ahead of print].

Mitochondria and plastids import thousands of proteins. Their experimental localisation remains a frequent task, but can be resource-intensive and sometimes impossible. Hence, hundreds of studies make use of algorithms that predict a localisation based on a protein's sequence. Their reliability across evolutionary diverse species is unknown. Here, we evaluate the performance of common algorithms (TargetP, Localizer and WoLFPSORT) for four photosynthetic eukaryotes (Arabidopsis thaliana, Zea mays, Physcomitrium patens, and Chlamydomonas reinhardtii) for which experimental plastid and mitochondrial proteome data is available, and 171 eukaryotes using orthology inferences. The match between predictions and experimental data ranges from 75% to as low as 2%. Results worsen as the evolutionary distance between training and query species increases, especially for plant mitochondria for which performance borders on random sampling. Specificity, sensitivity and precision analyses highlight cross-organelle errors and uncover the evolutionary divergence of organelles as the main driver of current performance issues. The results encourage to train the next generation of neural networks on an evolutionary more diverse set of organelle proteins for optimizing performance and reliability.

RevDate: 2024-11-09
CmpDate: 2024-11-09

Liu R, Ma T, Li Y, et al (2024)

Genomic Identification and Expression Analysis of Regulator of Chromosome Condensation 1-Domain Protein Family in Maize.

International journal of molecular sciences, 25(21): pii:ijms252111437.

Abiotic stress affects the growth and development of maize (Zea mays). The regulator of chromosome condensation 1 (RCC1)-containing proteins (RCPs) plays crucial roles in plant growth and development and response to abiotic stresses. However, a comprehensive analysis of the maize RCP family has not been reported in detail. This study presents a systematic bioinformatics analysis of the ZmRCP family, identifying a total of 30 members distributed across nine chromosomes. The physicochemical properties and cis-acting elements in the promoters of ZmRCP members are predicted. The results of subcellular localization showed that ZmRCP3 and ZmRCP10 are targeted to mitochondria and ZmRCP2 is localized in the nucleus. A heatmap of expression levels among family members under abiotic stress conditions revealed varying degrees of induced expression, and the expression levels of 10 ZmRCP members were quantified using RT-qPCR under abiotic stress and plant hormone treatments. The results showed that ZmRCP members exhibit induced or inhibited responses to these abiotic stresses and plant hormones. These results contribute to a better understanding of the evolutionary history and potential role of the ZmRCP family in mediating responses to abiotic stress in maize.

RevDate: 2024-11-06
CmpDate: 2024-11-06

Berrissou C, Cognat V, Koechler S, et al (2024)

Extensive import of nucleus-encoded tRNAs into chloroplasts of the photosynthetic lycophyte, Selaginella kraussiana.

Proceedings of the National Academy of Sciences of the United States of America, 121(46):e2412221121.

Over the course of evolution, land plant mitochondrial genomes have lost many transfer RNA (tRNA) genes and the import of nucleus-encoded tRNAs is essential for mitochondrial protein synthesis. By contrast, plastidial genomes of photosynthetic land plants generally possess a complete set of tRNA genes and the existence of plastidial tRNA import remains a long-standing question. The early vascular plants of the Selaginella genus show an extensive loss of plastidial tRNA genes while retaining photosynthetic capacity, and represent an ideal model for answering this question. Using purification, northern blot hybridization, and high-throughput tRNA sequencing, a global analysis of total and plastidial tRNA populations was undertaken in Selaginella kraussiana. We confirmed the expression of all plastidial tRNA genes and, conversely, observed that nucleus-encoded tRNAs corresponding to these plastidial tRNAs were generally excluded from the chloroplasts. We then demonstrated a selective and differential plastidial import of around forty nucleus-encoded tRNA species, likely compensating for the insufficient coding capacity of plastidial-encoded tRNAs. In-depth analysis revealed differential import of tRNA isodecoders, leading to the identification of specific situations. This includes the expression and import of nucleus-encoded tRNAs expressed from plastidial or bacterial-like genes inserted into the nuclear genome. Overall, our results confirm the existence of molecular processes that enable tRNAs to be selectively imported not only into mitochondria, as previously described, but also into chloroplasts, when necessary.

RevDate: 2024-11-01

Keeney JG, Astling D, Andries V, et al (2024)

Olduvai domain expression downregulates mitochondrial pathways: implications for human brain evolution and neoteny.

bioRxiv : the preprint server for biology pii:2024.10.21.619278.

Encoded by the NBPF gene family, Olduvai (formerly DUF1220) protein domains have undergone the largest human lineage-specific copy number expansion of any coding region in the genome. Olduvai copy number shows a linear relationship with several brain size-related measures and cortical neuron number among primates and with normal and disease-associated (micro- and macrocephaly) variation in brain size in human populations. While Olduvai domains have been shown to promote proliferation of neural stem cells, the mechanism underlying such effects has remained unclear. Here, we investigate the function of Olduvai by transcriptome and proteome analyses of cells overexpressing NBPF1 , a gene encoding 7 Olduvai domains. Our results from both RNAseq and mass spectrometry approaches suggest a potential downregulation of mitochondria. In our proteomics study, a Gene Ontology (GO) enrichment analysis for the downregulated proteins revealed a striking overrepresentation of the biological process related to the mitochondrial electron transport chain (p value: 1.81e-11) and identified deregulation of the NADH dehydrogenase activity (p value: 2.43e-11) as the primary molecular function. We verify the reduction of apparent mitochondria via live-cell imaging experiments. Given these and previous Olduvai findings, we suggest that the Olduvai-mediated, dosage-dependent reduction in available energy via mitochondrial downregulation may have resulted in a developmental slowdown such that the neurogenic window among primates, and most extremely in humans, was expanded over a greater time interval, allowing for production of greater numbers of neurons and a larger brain. We further suggest that such a slowdown may extend to other developmental processes that also exhibit neotenic features.

RevDate: 2024-11-02
CmpDate: 2024-11-02

Leka KP, JG Wideman (2024)

An introduction to comparative genomics, EukProt, and the reciprocal best hit (RBH) method for bench biologists: Ancestral phosphorylation of Tom22 in eukaryotes as a case study.

Methods in enzymology, 707:209-234.

Comparative genomics is a useful approach for hypothesis generation for future functional investigations at the bench. However, most bench biologists shy away from computational methods. Here we reintroduce the simple but extremely effective Reciprocal Best Hit method for inferring protein orthologues. Because taxon set delimitation is perhaps the most important step in comparative genomics, we introduce The Comparative Set, a taxonomically representative subset of EukProt, a comprehensive eukaryotic predicted proteome database. After introducing the basic methods, we provide a step-by-step guide, including screen shots, for a case study on collecting Tom22 sequences from diverse eukaryotes. As an example of possible downstream analyses, we show that Tom22 proteins from diverse eukaryotes are likely regulated by conserved kinases at several sites. Though the sites evolve quickly, the processes and functions involved are likely ancestral and conserved across many eukaryotes.

RevDate: 2024-11-03
CmpDate: 2024-10-30

Barcytė D, Jaške K, Pánek T, et al (2024)

A cryptic plastid and a novel mitochondrial plasmid in Leucomyxa plasmidifera gen. and sp. nov. (Ochrophyta) push the frontiers of organellar biology.

Open biology, 14(10):240022.

Complete plastid loss seems to be very rare among secondarily non-photosynthetic eukaryotes. Leukarachnion sp. PRA-24, an amoeboid colourless protist related to the photosynthetic algal class Synchromophyceae (Ochrophyta), is a candidate for such a case based on a previous investigation by transmission electron microscopy. Here, we characterize this organism in further detail and describe it as Leucomyxa plasmidifera gen. et sp. nov., additionally demonstrating it is the first known representative of a broader clade of non-photosynthetic ochrophytes. We recovered its complete plastid genome, exhibiting a reduced gene set similar to plastomes of other non-photosynthetic ochrophytes, yet being even more extreme in sequence divergence. Identification of components of the plastid protein import machinery in the L. plasmidifera transcriptome assembly corroborated that the organism possesses a cryptic plastid organelle. According to our bioinformatic reconstruction, the plastid contains a unique combination of biosynthetic pathways producing haem, a folate precursor and tocotrienols. As another twist to its organellar biology, L. plasmidifera turned out to contain an unusual long insertion in its mitogenome related to a newly discovered mitochondrial plasmid exhibiting unprecedented features in terms of its size and coding capacity. Combined, our work uncovered further striking outcomes of the evolutionary course of semiautonomous organelles in protists.

RevDate: 2024-10-29

Deconinck A, Madalone O, C Willett (2024)

Absence of heterosis for hypoxia tolerance in F1 hybrids of Tigriopus californicus.

The Journal of heredity pii:7848484 [Epub ahead of print].

Hybridization produces a range of outcomes from advantageous to disadvantageous, and a goal of genetic research is to understand the gene interactions that generate these outcomes. Interactions between cytoplasmic elements, such as mitochondria, and the nucleus may be particularly vulnerable to accruing disadvantageous combinations as a result of their different rates of evolution. However, mitonuclear incompatibilities often do not have an observable effect until the F2 and later generations. We used Tigriopus californicus, a model system for mitonuclear incompatibilities that is also known for exhibiting heterosis in the F1 generation, to test whether hypoxia was more stressful for mitonuclear interactions than other environmental stressors. We generated 284 parental and 436 F1 hybrids from four population crosses (720 total) and compared parental and F1 populations for hypoxia tolerance. We observed that, on average, F1 hybrids were less likely to survive a hypoxia stress test than parental populations (Parental:F1 coefficients ranged from -0.04 to 0.14 with none significantly different from 0). This suggests that hypoxia may be a particularly intense stressor for mitonuclear coordination, and that hybridization outcomes vary by trait.

RevDate: 2024-10-31
CmpDate: 2024-10-29

Büttiker P, Boukherissa A, Weissenberger S, et al (2024)

Cognitive Impact of Neurotropic Pathogens: Investigating Molecular Mimicry through Computational Methods.

Cellular and molecular neurobiology, 44(1):72.

Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein-protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.

RevDate: 2024-10-30
CmpDate: 2024-10-28

Cheng YK, Zhang Y, Zhang ZY, et al (2024)

Biological characteristics and functions of a novel glutamate dehydrogenase from Trichinella spiralis.

Parasite (Paris, France), 31:65.

Glutamate dehydrogenase (GDH) plays an important role in the metabolism of organisms. Its high abundance in mitochondria in particular highlights its core role in cellular physiological processes. GDH catalyzes the mutual conversion between L-glutamic acid and α-ketoglutaric acids. At the same time, this transformation is accompanied by the oxidation-reduction of NAD(H) or NADP(H). This process not only helps to link amino acid metabolism with sugar metabolism, but also helps maintain the balance of intracellular pH and nitrogen homeostasis. In this study, a novel Trichinella spiralis glutamate dehydrogenase (TsGDH) was cloned, expressed and identified. The results revealed that TsGDH was expressed at various stages of development of the nematode T. spiralis, with higher expression levels in the adult worm stage, and was mainly localized in the cuticle, muscular layer, stichosome and female intrauterine embryos. After RNAi treatment, larval natural TsGDH enzyme activity was obviously reduced, and metabolism, molting, growth and reproduction were also significantly inhibited. The results indicate that TsGDH plays an important role in the development and survival of T. spiralis, and it may be a potential molecular target of anti-Trichinella vaccines and drugs.

RevDate: 2024-10-28
CmpDate: 2024-10-26

Zhu K, Zhang Y, Shen W, et al (2024)

Genome-Wide Analysis and Expression Profiling of Glyoxalase Gene Families Under Abiotic Stresses in Cucumber (Cucumis sativus L.).

International journal of molecular sciences, 25(20):.

The glyoxalase pathway, consisting of glyoxalase I (GLYI) and glyoxalase II (GLYII), is an enzymatic system that converts cytotoxic methylglyoxal to non-toxic S-D-lactoylglutathione. Although the GLY gene family has been analyzed in Arabidopsis, rice, grape, cabbage, and soybean, cucumber studies are lacking. Here, we analyzed the cucumber GLY gene family, identifying 13 CsGLYI and 2 CsGLYII genes. Furthermore, we investigated the physicochemical properties, phylogenetic relationships, chromosomal localization and colinearity, gene structure, conserved motifs, cis-regulatory elements, and protein-protein interaction networks of the CsGLY family. They were primarily localized in the cytoplasm, chloroplasts, and mitochondria, with a minor presence in the nucleus. The classification of CsGLYI and CsGLYII genes into five classes closely resembled the homologous genes in Arabidopsis and soybean. Additionally, hormone-responsive elements dominated the promoter region of GLY genes, alongside light- and stress-responsive elements. The predicted interaction proteins of CsGLYIs and CsGLYIIs exerted a significant role in cellular respiration, amino acid synthesis, and metabolism, as well as methylglyoxal catabolism. In addition, the expression profiles of GLY genes were distinct in different tissues of cucumber as well as under diverse abiotic stresses. This study is conducive to the further exploration of the functional diversity among glyoxalase genes and the mechanisms of stress responses in cucumber.

RevDate: 2024-10-28
CmpDate: 2024-10-26

Li J, Ma M, Zeng T, et al (2024)

Genome-Wide Identification of the Peanut ASR Gene Family and Its Expression Analysis under Abiotic Stress.

International journal of molecular sciences, 25(20):.

Peanut (Arachis hypogaea L.) is one of the most important oil and food legume crops worldwide. ASR (abscisic acid, stress, ripening) plays extremely important roles in plant growth and development, fruit ripening, pollen development, and stress. Here, six ASR genes were identified in peanut. Structural and conserved motif analyses were performed to identify common ABA/WDS structural domains. The vast majority of ASR genes encoded acidic proteins, all of which are hydrophilic proteins and localized on mitochondria and nucleus, respectively. The cis-element analysis revealed that some cis-regulatory elements were related to peanut growth and development, hormone, and stress response. Under normal growth conditions, AhASR4 and AhASR5 were expressed in all tissues of peanut plants. Quantitative real-time PCR (qRT-PCR) results indicated that peanut ASR genes exhibited complex expression patterns in response to abiotic stress. Notably, under drought and cadmium (Cd) stress, the expression levels of AhASR4 and AhASR5 were significantly upregulated, suggesting that these genes may play a crucial role in the peanut plant's resistance to such stressors. These results provide a theoretical basis for studying the evolution, expression, and function of the peanut ASR gene family and will provide valuable information in the identification and screening of genes for peanut stress tolerance breeding.

RevDate: 2024-10-28
CmpDate: 2024-10-26

Indo HP, Chatatikun M, Nakanishi I, et al (2024)

The Roles of Mitochondria in Human Being's Life and Aging.

Biomolecules, 14(10):.

The universe began 13.8 billion years ago, and Earth was born 4.6 billion years ago. Early traces of life were found as soon as 4.1 billion years ago; then, ~200,000 years ago, the human being was born. The evolution of life on earth was to become individual rather than cellular life. The birth of mitochondria made this possible to be the individual life. Since then, individuals have had a limited time of life. It was 1.4 billion years ago that a bacterial cell began living inside an archaeal host cell, a form of endosymbiosis that is the development of eukaryotic cells, which contain a nucleus and other membrane-bound compartments. The bacterium started to provide its host cell with additional energy, and the interaction eventually resulted in a eukaryotic cell, with both archaeal (the host cell) and bacterial (mitochondrial) origins still having genomes. The cells survived high concentrations of oxygen producing more energy inside the cell. Further, the roles of mitochondria in human being's life and aging will be discussed.

RevDate: 2024-11-04

Liu X, Liu N, Jing X, et al (2024)

Genomic and transcriptomic perspectives on the origin and evolution of NUMTs in Orthoptera.

Molecular phylogenetics and evolution, 201:108221 pii:S1055-7903(24)00213-6 [Epub ahead of print].

Nuclear mitochondrial pseudogenes (NUMTs) result from the transfer of mitochondrial DNA (mtDNA) to the nuclear genome. NUMTs, as "frozen" snapshots of mitochondria, can provide insights into diversification patterns. In this study, we analyzed the origins and insertion frequency of NUMTs using genome assembly data from ten species in Orthoptera. We found divergences between NUMTs and contemporary mtDNA in Orthoptera ranging from 0 % to 23.78 %. The results showed that the number of NUMT insertions was significantly positively correlated with the content of transposable elements in the genome. We found that 39.09 %-68.65 % of the NUMTs flanking regions (2,000 bp) contained retrotransposons, and more NUMTs originated from mitochondrial rDNA regions. Based on the analysis of the mitochondrial transcriptome, we found a potential mechanism of NUMT integration: mitochondrial transcripts are reverse transcribed into double-stranded DNA and then integrated into the genome. The probability of this mechanism occurring accounts for 0.30 %-1.02 % of total mitochondrial nuclear transfer events. Finally, based on the phylogenetic tree constructed using NUMTs and contemporary mtDNA, we provide insights into ancient evolutionary events such as species-specific "autaponumts" and "synaponumts" shared among different species, as well as post-integration duplication events.

RevDate: 2024-10-20
CmpDate: 2024-10-17

Stefano GB, Weissenberger S, Ptacek R, et al (2024)

Viruses and Mitochondrial Dysfunction in Neurodegeneration and Cognition: An Evolutionary Perspective.

Cellular and molecular neurobiology, 44(1):68.

Mitochondria, the cellular powerhouses with bacterial evolutionary origins, play a pivotal role in maintaining neuronal function and cognitive health. Several viruses have developed sophisticated mechanisms to target and disrupt mitochondrial function which contribute to cognitive decline and neurodegeneration. The interplay between viruses and mitochondria might be traced to their co-evolutionary history with bacteria and may reflect ancient interactions that have shaped modern mitochondrial biology.

RevDate: 2024-10-18

Bakhoum AJS, Marigo AM, Poonlaphdecha S, et al (2024)

Ultrastructural Characteristics of the Mature Spermatozoon of Artyfechinostomum malayanum (Digenea: Echinostomatidae), an Intestinal Parasite of Rattus norvegicus (Rodentia: Muridae) in Vietnam.

Animals : an open access journal from MDPI, 14(19):.

The study of sperm characteristics has proven useful for elucidating interrelationships in several groups of Platyhelminthes, such as digeneans. Thus, in the present work, the ultrastructural organization of the mature spermatozoon of the digenean Artyfechinostomum malayanum (Echinostomatidae), a parasite of Rattus norvegicus (Rodentia: Muridae) from Dong Thap Province, Vietnam, was investigated for the first time using transmission electron microscopy. The male gamete of A. malayanum exhibits two axonemes of different lengths, showing the 9 + '1' pattern of the Trepaxonemata, a nucleus, two mitochondria, two lateral expansions, two bundles of parallel cortical microtubules, external ornamentation, spine-like bodies, and granules of glycogen. Thus, the mature spermatozoon follows a Type V sperm model proposed for digeneans. We also highlight some noteworthy characteristics in Echinostomatidae with possible phylogenetic implications, such as two lateral expansions in the anterior region of the spermatozoon and two mitochondria.

RevDate: 2024-10-19
CmpDate: 2024-10-16

Wang Y, Shi Y, Li H, et al (2024)

Whole Genome Identification and Biochemical Characteristics of the Tilletia horrida Cytochrome P450 Gene Family.

International journal of molecular sciences, 25(19):.

Rice kernel smut caused by the biotrophic basidiomycete fungus Tilletia horrida causes significant yield losses in hybrid rice-growing areas around the world. Cytochrome P450 (CYP) enzyme is a membrane-bound heme-containing monooxygenase. In fungi, CYPs play a role in cellular metabolism, adaptation, pathogenicity, decomposition, and biotransformation of hazardous chemicals. In this study, we identified 20 CYP genes based on complete sequence analysis and functional annotation from the T. horrida JY-521 genome. The subcellular localization, conserved motifs, and structures of these 20 CYP genes were further predicted. The ThCYP genes exhibit differences in gene structures and protein motifs. Subcellular localization showed that they were located in the plasma membrane, cytoplasm, nucleus, mitochondria, and extracellular space, indicating that they had multiple functions. Some cis-regulatory elements related to stress response and plant hormones were found in the promoter regions of these genes. Protein-protein interaction (PPI) analysis showed that several ThCYP proteins interact with multiple proteins involved in the ergosterol pathway. Moreover, the expression of 20 CYP genes had different responses to different infection time points and underwent dynamic changes during T. horrida JY-521 infection, indicating that these genes were involved in the interaction with rice and their potential role in the pathogenic mechanism. These results provided valuable resources for elucidating the structure of T. horrida CYP family proteins and laid an important foundation for further research of their roles in the pathogenesis.

RevDate: 2024-10-15

Storer ISR, Sastré-Velásquez LE, Easter T, et al (2024)

Shining a light on the impact of antifungals on Aspergillus fumigatus subcellular dynamics through fluorescence imaging.

Antimicrobial agents and chemotherapy [Epub ahead of print].

Fluorescent proteins (FPs) are indispensable tools used for molecular imaging, single-cell dynamics, imaging in infection models, and more. However, next-generation FPs have yet to be characterized in Aspergillus. Here, we characterize 18 FPs in the pathogenic filamentous fungus Aspergillus fumigatus spanning the visible light spectrum. We report on in vivo FP brightness in hyphal and spore morphotypes and show how a fluoropyrimidine-based selection system can be used to iteratively introduce four distinct FPs enabling the simultaneous visualization of the cell membrane, mitochondria, peroxisomes, and vacuoles. Using this strain, we describe and compare the dynamic responses of organelles to stresses induced by voriconazole, amphotericin B, and the novel antifungal drugs olorofim and manogepix. The expansion to the fluorescent genetic toolbox will overcome boundaries in research applications that involve fluorescence imaging in filamentous fungi.

RevDate: 2024-10-12

Greenway R, De-Kayne R, Brown AP, et al (2024)

Integrative analyses of convergent adaptation in sympatric extremophile fishes.

Current biology : CB pii:S0960-9822(24)01238-7 [Epub ahead of print].

The evolution of independent lineages along replicated environmental transitions frequently results in convergent adaptation, yet the degree to which convergence is present across multiple levels of biological organization is often unclear. Additionally, inherent biases associated with shared ancestry and variation in selective regimes across geographic replicates often pose challenges for confidently identifying patterns of convergence. We investigated a system in which three species of poeciliid fishes sympatrically occur in a toxic spring rich in hydrogen sulfide (H2S) and an adjacent nonsulfidic stream to examine patterns of adaptive evolution across levels of biological organization. We found convergence in morphological and physiological traits and genome-wide patterns of gene expression among all three species. In addition, there were shared signatures of selection on genes encoding H2S toxicity targets in the mitochondrial genomes of each species. However, analyses of nuclear genomes revealed neither evidence for substantial genomic islands of divergence around genes involved in H2S toxicity and detoxification nor substantial congruence of strongly differentiated regions across population pairs. These non-convergent, heterogeneous patterns of genomic divergence may indicate that sulfide tolerance is highly polygenic, with shared allele frequency shifts present at many loci with small effects along the genome. Alternatively, H2S tolerance may involve substantial genetic redundancy, with non-convergent, lineage-specific variation at multiple loci along the genome underpinning similar changes in phenotypes and gene expression. Overall, we demonstrate variability in the extent of convergence across organizational levels and highlight the challenges of linking patterns of convergence across scales.

RevDate: 2024-10-24
CmpDate: 2024-10-11

Princepe D, MAM de Aguiar (2024)

Nuclear compensatory evolution driven by mito-nuclear incompatibilities.

Proceedings of the National Academy of Sciences of the United States of America, 121(42):e2411672121.

Mitochondrial function relies on the coordinated expression of mitochondrial and nuclear genes, exhibiting remarkable resilience despite high mitochondrial mutation rates. The nuclear compensation mechanism suggests deleterious mitochondrial alleles drive compensatory nuclear mutations to preserve mito-nuclear compatibility. However, prevalence and factors conditioning this phenomenon remain debated due to its conflicting evidence. Here, we investigate how mito-nuclear incompatibilities impact substitutions in a model for species radiation. Mating success depends on genetic compatibility (nuclear DNA) and spatial proximity. Populations evolve from partially compatible mito-nuclear states, simulating mitochondrial DNA (mtDNA) introgression. Mutations do not confer advantages nor disadvantages, but individual fecundity declines with increasing incompatibilities, selecting for mito-nuclear coordination. We find that selection for mito-nuclear compatibility affects each genome differently based on their initial state. In compatible gene pairs, selection reduces substitutions in both genomes, while in incompatible nuclear genes, it consistently promotes compensation, facilitated by more mismatches. Interestingly, high mitochondrial mutation rates can reduce nuclear compensation by increasing mtDNA rectification, while substitutions in initially compatible nuclear gene are boosted. Finally, the presence of incompatibilities accelerates species radiation, but equilibrium richness is not directly correlated to substitution rates, revealing the complex dynamics triggered by mitochondrial introgression and mito-nuclear coevolution. Our study provides a perspective on nuclear compensation and the role of mito-nuclear incompatibilities in speciation by exploring extreme scenarios and identifying trends that empirical data alone cannot reveal. We emphasize the challenges in detecting these dynamics and propose analyzing specific genomic signatures could shed light on this evolutionary process.

RevDate: 2024-10-13
CmpDate: 2024-10-11

Li Y, Thomas GWC, Richards S, et al (2024)

Rapid evolution of mitochondrion-related genes in haplodiploid arthropods.

BMC biology, 22(1):229.

BACKGROUND: Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes.

RESULTS: We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants.

CONCLUSIONS: Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans.

RevDate: 2024-10-23

Korotkevich E, Conrad DN, Gartner ZJ, et al (2024)

Selection promotes age-dependent degeneration of the mitochondrial genome.

bioRxiv : the preprint server for biology.

Somatic mutations in mitochondrial genomes (mtDNA) accumulate exponentially during aging. Using single cell sequencing, we characterize the spectrum of age-accumulated mtDNA mutations in mouse and human liver and identify directional forces that accelerate the accumulation of mutations beyond the rate predicted by a neutral model. "Driver" mutations that give genomes a replicative advantage rose to high cellular abundance and carried along "passenger" mutations, some of which are deleterious. In addition, alleles that alter mtDNA-encoded proteins selectively increased in abundance overtime, strongly supporting the idea of a "destructive" selection that favors genomes lacking function. Overall, this combination of selective forces acting in hepatocytes promotes somatic accumulation of mutations in coding regions of mtDNA that are otherwise conserved in evolution. We propose that these selective processes could contribute to the population prevalence of mtDNA mutations, accelerate the course of heteroplasmic mitochondrial diseases and promote age-associated erosion of the mitochondrial genome.

RevDate: 2024-10-23

Smith TB, Kopajtich R, Demain LAM, et al (2024)

Biallelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered intrinsic and extrinsic apoptosis and a Perrault syndrome-spectrum phenotype.

medRxiv : the preprint server for health sciences.

The mitoribosome synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders, and frequently show combined oxidative phosphorylation deficiency. Here, we describe five unrelated individuals with biallelic variants in the DAP3 nuclear gene encoding mitoribosomal small subunit 29 (MRPS29), with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein levels, and consequently decreased levels of additional protein components of the mitoribosomal small subunit, associated with a combined complex I and IV deficiency. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression, and partially rescued protein levels of MRPS7, MRPS9 and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants. Protein modelling suggested that DAP3 disease-associated missense variants can impact ADP binding, and in vitro assays demonstrated DAP3 variants can consequently reduce both intrinsic and extrinsic apoptotic sensitivity, DAP3 thermal stability and DAP3 GTPase activity. Our study presents genetic and functional evidence that biallelic variants in DAP3 result in a multisystem disorder of combined oxidative phosphorylation deficiency with pleiotropic presentations, consistent with mitochondrial dysfunction.

RevDate: 2024-10-09
CmpDate: 2024-10-06

Zhu L, Diao S, Li T, et al (2024)

Deciphering the multi- partite mitochondrial genome of Crataegus pinnatifida: insights into the evolution and genetics of cultivated Hawthorn.

BMC plant biology, 24(1):929.

Flowering plant (angiosperm) mitochondrial genomes are remarkably dynamic in their structures. We present the complete mitochondrial genome of hawthorn (Crataegus pinnatifida Bunge), a shrub that bears fruit and is celebrated for its extensive medicinal history. We successfully assembled the hawthorn mitogenome utilizing the PacBio long-read sequencing technique, which yielded 799,862 reads, and the Illumina novaseq6000 sequencing platform, which producing 6.6 million raw paired reads. The C. pinnatifida mitochondria sequences encompassed a total length of 440,295 bp with a GC content of 45.42%. The genome annotates 54 genes, including 34 that encode proteins, 17 that encode tRNA, and three genes for rRNA. A fascinating interplay was observed between the chloroplast and mitochondrial genomes, which share 17 homologous sequences sequences that rotal 1,933 bp. A total of 134 SSRs, 22 tandem repeats and 42 dispersed repeats were identified in the mitogenome. Four conformations of C. pinnatifida mitochondria sequences recombination were verified through PCR experiments and Sanger sequencing, and C. pinnatifida mitogenome is more likely to be assembled into three circular-mapping chromosomes. All the RNA editing sites that were identified C-U edits, which predominantly occurred at the first and second positions of the codons. Phylogenetic and collinearity analyses identified the evolutionary trajectory of C. pinnatifida, which reinforced the genetic identity of the hawthorn section. This unveiling of the unique multi-partite structure of the hawthorn mitogenome offers a foundational reference for future study into the evolution and genetics of C. pinnatifida.

RevDate: 2024-10-08
CmpDate: 2024-10-05

Tseng WW, Chu CH, Lee YJ, et al (2024)

Metabolic regulation of mitochondrial morphologies in pancreatic beta cells: coupling of bioenergetics and mitochondrial dynamics.

Communications biology, 7(1):1267.

Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated levels of blood glucose. To elucidate the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and graph-based network analysis. The aim is to determine the mechanism that regulates mitochondrial morphology and balances metabolic demands in pancreatic beta cells. A minimalistic differential equation-based model for beta cells is constructed that includes glycolysis, oxidative phosphorylation, calcium dynamics, and fission/fusion dynamics, with ATP synthase flux and proton leak flux as main regulators of mitochondrial dynamics. The model shows that mitochondrial fission occurs in response to hyperglycemia, starvation, ATP synthase inhibition, uncoupling, and diabetic conditions, in which the rate of proton leakage exceeds the rate of mitochondrial ATP synthesis. Under these metabolic challenges, the propensities of tip-to-tip fusion events simulated from the microscopy images of the mitochondrial networks are lower than those in the control group and prevent the formation of mitochondrial networks. The study provides a quantitative framework that couples bioenergetic regulation with mitochondrial dynamics, offering insights into how mitochondria adapt to metabolic challenges.

RevDate: 2024-10-04

Piselli C (2024)

How to isolate channel-forming membrane proteins using the E. coli expression system.

Nature protocols [Epub ahead of print].

The recombinant expression, isolation and characterization of pore-forming proteins is one of the most commonly used strategies for understanding the permeability properties of the biological membrane into which they are embedded. This protocol describes how to quantify the expression of your protein of interest and use this information to optimize its production using the Escherichia coli strain BL21Gold(de3)ΔABCF. It explains with a step-by-step approach how to separate the bacterial compartments according to their solubility and how to extract your protein of interest in its native conformation using detergent solutions. Finally, it describes how to improve its purity via ion-exchange chromatography and insert the purified porins into outer membrane vesicles, from which they can be copurified. The protocol is simpler and less empirical than those described for most channel-forming membrane proteins and also provides a solid foundation for the isolation of soluble proteins. Several parameters can be optimized on a case-by-case basis: expression time and temperature, concentration of the inducer, nature and concentration of the detergent, incubation time and temperature, pH and ionic strength of the purification buffers. This protocol is effective with prokaryotic channel-forming membrane proteins and can be employed for the production of pore-forming proteins from chloroplasts, mitochondria or eukaryotes in general. With minor optimization, this protocol can be adapted for the isolation of receptors, carrier, pumps or any other membrane-active proteins.

RevDate: 2024-10-05
CmpDate: 2024-10-02

Tronik-Le Roux D, Daouya M, Poras I, et al (2024)

HLA-G neo-expression modifies genetic programs governing tumor cell lines.

Cancer immunology, immunotherapy : CII, 73(12):247.

The development of immunotherapies has proved to be clinically encouraging to re-establish the immune function modified by the expression of immune inhibitory molecules in tumors. However, there are still patients with poor survival rates following treatment. The elucidation of molecular mechanisms triggered by the neo-expression of particular IC in tumors would constitute a major step toward better understanding tumor evolution and would help to design future clinical protocols. To this end, we investigate the modifications triggered by the neo-expression of the immune checkpoints HLA-G in ccRCC tumor cells. We demonstrate, for the first time, that HLA-G modifies key genes implicated mainly in tumor development, angiogenesis, calcium flow and mitochondria dynamics. The involvement of HLA-G on the expression of genes belonging to these pathways such as ADAM-12, NCAM1 and NRP1 was confirmed by the CRISPR/Cas9-mediated edition of HLA-G. The data reveal multifaceted roles of HLA-G in tumor cells which are far beyond the well-known function of HLA-G in the immune anti-tumor response. This warrants further investigation of HLA-G and these new partners in tumors of different origin so as to propose future new treatments to improve health patient's outcome.

RevDate: 2024-10-28
CmpDate: 2024-10-28

Zouaoui S, R Rouabhi (2024)

Lysosomal disruption, mitochondrial impairment, histopathological and oxidative stress in rat's nervous system after exposure to a neonicotinoid (imidacloprid).

Environmental science and pollution research international, 31(49):59472-59489.

Imidacloprid (IMI), a neonicotinoid pesticide, has been widely used due to its high efficiency against insect pests. However, its prolonged exposure may pose significant risks to non-target organisms, including mammals. Recent studies have raised concerns about its potential neurotoxicity, yet the underlying mechanisms remain poorly understood. This study aimed to assess the neurotoxic effects of chronic Imidacloprid exposure in Wistar rats, focusing on oxidative stress, mitochondrial dysfunction, and lysosomal disruption. Wistar rats were orally administered two doses of Imidacloprid (5 mg/kg and 50 mg/kg body weight) for three months. Neurotoxic effects were assessed by measuring key biochemical markers such as the enzymatic activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione S-transferase (GST). Non-enzymatic markers, including glutathione (GSH) levels and malondialdehyde (MDA) index, were also evaluated. Mitochondrial function was assessed by analyzing oxygen consumption, swelling, and membrane permeability and histopathological changes. Lysosomal stability was examined using the Neutral Red Retention Time (NRRT) assay. Neutral red is a dye that accumulates in the acidic environment of lysosomes. Healthy lysosomes retain the dye, while compromised lysosomes lose it, indicating destabilization. By measuring the amount of neutral red retained in lysosomes, the NRRT assay assesses lysosomal integrity. Lysosomal pH variations were also monitored to evaluate functional changes. Microscopic analysis provided insight into structural changes in lysosomes and other cell components. Lysosomal destabilization was further confirmed by morphological alterations observed through light microscopy, revealing a progressive, time-dependent degeneration of lysosomal structures, including lysosomal expansion, neutral red dye leakage, and cell rounding. These changes reflected a temporal evolution of lysosomal damage, progressing from minor structural disruptions to more severe alterations as exposure continued, observable at the microscopic level. During the study, clinical observations of intoxicated rats included symptoms such as lethargy, reduced activity levels, and impaired motor coordination. High-dose Imidacloprid exposure led to noticeable behavioral changes, including decreased exploratory behavior and altered grooming patterns. Additionally, signs of neurotoxic effects, such as tremors or ataxia, were observed in the rats exposed to the higher dose, reflecting the systemic impact of chronic pesticide exposure. The results revealed a significant decrease in the enzymatic activities of CAT, GPx, and SOD, accompanied by an increase in GST activity. A notable reduction in glutathione levels and a rise in MDA index were observed, indicating enhanced oxidative stress in the brain. Mitochondrial impairment was evidenced by disturbances in oxygen consumption, increased swelling, and altered membrane permeability. Lysosomal destabilization was confirmed by reduced retention of neutral red dye, structural changes in lysosomes, and a significant rise in lysosomal pH in the IMI-exposed groups. In addition, the histopathological features indicate that imidacloprid at the given dose and exposure duration may have caused notable neurotoxic effects in Wistar rat brain tissue. Chronic exposure to Imidacloprid induces oxidative stress, mitochondrial dysfunction, lysosomal disruption and histopathological alterations in the central nervous system of Wistar rats. These findings provide valuable insights into the neurotoxic mechanisms of neonicotinoid pesticides, highlighting the need for further research to understand the long-term effects of Imidacloprid exposure on mammalian health.

RevDate: 2024-10-03
CmpDate: 2024-09-29

Ahmad F, Abdullah M, Khan Z, et al (2024)

Genome-wide analysis and prediction of chloroplast and mitochondrial RNA editing sites of AGC gene family in cotton (Gossypium hirsutum L.) for abiotic stress tolerance.

BMC plant biology, 24(1):888.

BACKGROUND: Cotton is one of the topmost fiber crops throughout the globe. During the last decade, abrupt changes in the climate resulted in drought, heat, and salinity. These stresses have seriously affected cotton production and significant losses all over the textile industry. The GhAGC kinase, a subfamily of AGC group and member of serine/threonine (Ser/Thr) protein kinases group and is highly conserved among eukaryotic organisms. The AGC kinases are compulsory elements of cell development, metabolic processes, and cell death in mammalian systems. The investigation of RNA editing sites within the organelle genomes of multicellular vascular plants, such as Gossypium hirsutum holds significant importance in understanding the regulation of gene expression at the post-transcriptional level.

METHODS: In present work, we characterized twenty-eight GhAGC genes in cotton and constructed phylogenetic tree using nine different species from the most primitive to the most recent.

RESULTS: In sequence logos analyses, highly conserved amino acid residues were found in G. hirsutum, G. arboretum, G. raimondii and A. thaliana. The occurrence of cis-acting growth and stress-related elements in the promoter regions of GhAGCs highlight the significance of these factors in plant development and abiotic stress tolerance. Ka/Ks levels demonstrated that purifying selection pressure resulting from segmental events was applied to GhAGC with little functional divergence. We focused on identifying RNA editing sites in G. hirsutum organelles, specifically in the chloroplast and mitochondria, across all 28 AGC genes.

CONCLUSION: The positive role of GhAGCs was explored by quantifying the expression in the plant tissues under abiotic stress. These findings help in understanding the role of GhAGC genes under abiotic stresses which may further be used in cotton breeding for the development of climate smart varieties in abruptly changing climate.

RevDate: 2024-10-01
CmpDate: 2024-09-29

Ye H, Liu H, Li H, et al (2024)

Complete mitochondrial genome assembly of Juglans regia unveiled its molecular characteristics, genome evolution, and phylogenetic implications.

BMC genomics, 25(1):894.

BACKGROUND: The Persian walnut (Juglans regia), an economically vital species within the Juglandaceae family, has seen its mitochondrial genome sequenced and assembled in the current study using advanced Illumina and Nanopore sequencing technology.

RESULTS: The 1,007,576 bp mitogenome of J. regia consisted of three circular chromosomes with a 44.52% GC content encoding 39 PCGs, 47 tRNA, and five rRNA genes. Extensive repetitive sequences, including 320 SSRs, 512 interspersed, and 83 tandem repeats, were identified, contributing to genomic complexity. The protein-coding sequences (PCGs) favored A/T-ending codons, and the codon usage bias was primarily shaped by selective pressure. Intracellular gene transfer occurred among the mitogenome, chloroplast, and nuclear genomes. Comparative genomic analysis unveiled abundant structure and sequence variation among J. regia and related species. The results of selective pressure analysis indicated that most PCGs underwent purifying selection, whereas the atp4 and ccmB genes had experienced positive selection between many species pairs. In addition, the phylogenetic examination, grounded in mitochondrial genome data, precisely delineated the evolutionary and taxonomic relationships of J. regia and its relatives. We identified a total of 539 RNA editing sites, among which 288 were corroborated by transcriptome sequencing data. Furthermore, expression profiling under temperature stress highlighted the complex regulation pattern of 28 differently expressed PCGs, wherein NADH dehydrogenase and ATP synthase genes might be critical in the mitochondria response to cold stress.

CONCLUSIONS: Our results provided valuable molecular resources for understanding the genetic characteristics of J. regia and offered novel perspectives for population genetics and evolutionary studies in Juglans and related woody species.

RevDate: 2024-09-28

Yazaki E, Uehara T, Sakamoto H, et al (2024)

Dinotoms possess two evolutionary distinct autophagy-related ubiquitin-like conjugation systems.

Protist, 175(6):126067 pii:S1434-4610(24)00059-2 [Epub ahead of print].

Autophagy is an intracellular degradation mechanism by which cytoplasmic materials are delivered to and degraded in the lysosome-fused autophagosome (autolysosome) and proposed to have been established at an early stage of eukaryotic evolution. Dinoflagellates harboring endosymbiotic diatoms (so-called "dinotoms"), which retain their own nuclei and mitochondria in addition to plastids, have been investigated as an intermediate toward the full integration of a eukaryotic phototroph into the host-controlled organelle (i.e., plastid) through endosymbiosis. Pioneering studies systematically evaluated the degree of host governance on several metabolic pathways in the endosymbiotic diatoms (ESDs). However, little attention has been paid to the impact of the endosymbiotic lifestyle on the autophagy operated in the ESDs. In this study, we searched for ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, and ATG12, which are required for autophagosome formation, in the RNA-seq data from dinotoms Durinskia baltica and Kryptoperidinium foliaceum. We detected two evolutionally distinct sets of the ATG proteins in the dinotom species, one affiliated with the dinoflagellate homologs and the other with the diatom homologs in phylogenetic analyses. The results suggest that the ATG proteins descended from the diatom taken up by the dinoflagellate host persist for autophagosome formation and, most likely, autophagy.

RevDate: 2024-09-30
CmpDate: 2024-09-28

Gambino G, Da Pozzo E, Salvetti A, et al (2024)

Planarian Mucus: A Novel Source of Pleiotropic Cytotoxic and Cytostatic Agents against Cancer Cells.

Biomolecules, 14(9):.

Biological evolution has generated a vast array of natural compounds produced by organisms across all domains. Among these, secondary metabolites, selected to enhance an organism's competitiveness in its natural environment, make them a reservoir for discovering new compounds with cytotoxic activity, potentially useful as novel anticancer agents. Slime secretions, the first barrier between epithelial surfaces and the surrounding environment, frequently contain cytotoxic molecules to limit the growth of parasitic organisms. Planarians, freshwater Triclads, continuously secrete a viscous mucus with multiple physiological functions. The chemical composition of planarian mucus has been only partially elucidated, and there are no studies reporting its cytotoxic or cytostatic effects. In this study, we developed a protocol for collecting mucus from Dugesia japonica specimens and we demonstrated that it inhibits the growth of cancer cells by activating cytostatic and ROS-dependent cytotoxic mechanisms inducing lipid droplet accumulation and mitochondrial membrane reorganization. Although further research is needed to identify the specific chemicals responsible for the anticancer activity of planarian mucus, this work opens up numerous research avenues aimed at better understanding the mechanisms of action of this product for potential therapeutic applications.

RevDate: 2024-09-29
CmpDate: 2024-09-27

Kubota K, Oishi M, Taniguchi E, et al (2024)

Mitochondrial phylogeny and distribution of cytoplasmic male sterility-associated genes in Beta vulgaris.

PloS one, 19(9):e0308551.

Cytoplasmic male sterility (CMS) is a mitochondrial-encoded trait that confers reproductive defects in males but not in females or any vegetative function. Why CMS is so often found in plants should be investigated from the viewpoint of mitochondrial phylogeny. Beta vulgaris, including the wild subspecies maritima and cultivated subspecies vulgaris (e.g., sugar beet), is known to be mitochondrially polymorphic, from which multiple CMS mitochondria have been found, but their evolutionary relationship has been obscure. We first refined the B. vulgaris reference mitochondrial genome to conduct a more accurate phylogenetic study. We identified mitochondrial single-nucleotide polymorphic sites from 600 B. vulgaris accessions. Principal component analysis, hierarchical clustering analysis, and creation of a phylogenetic tree consistently suggested that B. vulgaris mitochondria can be classified into several groups whose geographical distribution tends to be biased toward either the Atlantic or Mediterranean coasts. We examined the distribution of CMS-associated mitochondrial genes from Owen, E- and G-type CMS mitochondria. About one-third of cultivated beets had Owen-type CMS, which reflects the prevalence of using Owen-type CMS in hybrid breeding. Occurrence frequencies for each of the three CMS genes in wild beet were less than 4%. CMS genes were tightly associated with specific mitochondrial groups that are phylogenetically distinct, suggesting their independent origin. However, homologous sequences of the Owen type CMS gene occurred in several different mitochondrial groups, for which an intricate explanation is necessary. Whereas the origin of cultivated beet had been presumed to be Greece, we found an absence of Owen-type mitochondria in Greek accessions.

RevDate: 2024-10-11

Rodriguez E, Peng B, N Lane (2024)

Anaesthetics disrupt complex I-linked respiration and reverse the ATP synthase.

Biochimica et biophysica acta. Bioenergetics, 1866(1):149511 pii:S0005-2728(24)00481-X [Epub ahead of print].

The mechanism of volatile general anaesthetics has long been a mystery. Anaesthetics have no structural motifs in common, beyond lipid solubility, yet all exert a similar effect. The fact that the inert gas xenon is an anaesthetic suggests their common mechanism might relate to physical rather than chemical properties. Electron transfer through chiral proteins can induce spin polarization. Recent work suggests that anaesthetics dissipate spin polarization during electron transfer to oxygen, slowing respiration. Here we show that the volatile anaesthetics isoflurane and sevoflurane specifically disrupt complex I-linked respiration in the thoraces of Drosophila melanogaster, with less effect on maximal respiration. Suppression of complex I-linked respiration was greatest with isoflurane. Using high-resolution tissue fluorespirometry, we show that these anaesthetics simultaneously increase mitochondrial membrane potential, implying reversal of the ATP synthase. Inhibition of ATP synthase with oligomycin prevented respiration and increased membrane potential back to the maximal (LEAK state) potential. Magnesium-green fluorescence predicted a collapse in ATP availability following a single anaesthetic dose, consistent with ATP hydrolysis through reversal of the ATP synthase. Raised membrane potential corresponded to a rise in ROS flux, especially with isoflurane. Anaesthetic doses causing respiratory suppression were in the same range as those that induce anaesthesia, although we could not establish tissue concentrations. Our findings show that anaesthetics suppress complex I-linked respiration with concerted downstream effects. But we cannot explain why only mutations in complex I, and not elsewhere in the electron-transfer system, confer hypersensitivity to anaesthetics.

RevDate: 2024-09-24

Mendoza H, Lamb EA, Thomas J, et al (2024)

Comparative mitogenomic analysis of Sporisorium reilianum f. sp. zeae suggests recombination events during its evolutionary history.

Frontiers in physiology, 15:1264359.

INTRODUCTION: Modern understanding of the concept of genetic diversity must include the study of both nuclear and organellar DNA, which differ greatly in terms of their structure, organization, gene content and distribution. This study comprises an analysis of the genetic diversity of the smut fungus Sporisorium reilianum f. sp. zeae from a mitochondrial perspective.

METHODS: Whole-genome sequencing data was generated from biological samples of S. reilianum collected from different geographical regions. Multiple sequence alignment and gene synteny analysis were performed to further characterize genetic diversity in the context of mitogenomic polymorphisms.

RESULTS: Mitochondria of strains collected in China contained unique sequences. The largest unique sequence stretch encompassed a portion of cox1, a mitochondrial gene encoding one of the subunits that make up complex IV of the mitochondrial electron transport chain. This unique sequence had high percent identity to the mitogenome of the related species Sporisorium scitamineum and Ustilago bromivora.

DISCUSSION: The results of this study hint at potential horizontal gene transfer or mitochondrial genome recombination events during the evolutionary history of basidiomycetes. Additionally, the distinct polymorphic region detected in the Chinese mitogenome provides the ideal foundation to develop a diagnostic method to discern between mitotypes and enhance knowledge on the genetic diversity of this organism.

RevDate: 2024-09-23
CmpDate: 2024-09-22

Zhang YX, Fan X, Zhang M, et al (2024)

[Influence of Tis108 on GA content and expression of key enzyme GeCYP714A1 involved in GA deactivation of Gastrodia elata].

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 49(15):4007-4014.

To investigate the influence of the strigolactone inhibitor Tis108 on the growth of Gastrodia elata, this study treated G. elata tuber with Tis108 solution of 10 μmol·L~(-1) and measured the content of endogenous hormone gibberellin(GA) in the tuber. By using reverse transcription-polymerase chain reaction(RT-PCR) technology, the key enzyme GeCYP714A1 gene involved in GA deactivation was cloned. Bioinformatics analysis on the GeCYP714A1 gene was carried out by using ExPASy, SWISS-MODEL, MEGA, etc., and its expression levels in different parts of G. elata were determined. The results showed that after Tis108 treatment, GA content in G. elata tuber was significantly increased, and the transcription level of the GeCYP714A1 gene was significantly decreased. The full length of the coding region of the GeCYP714A1 gene is 1 173 bp, encoding 390 amino acids. The protein has a molecular weight of 44.85 kDa, a theoretical isoelectric point of 9.83, an instability index of 49.20, an aliphatic index of 89.03, and a grand average of hydropathicity of-0.235, classifying it as an unstable, basic, hydrophilic protein, and the GeCYP714A1 protein was localized in the mitochondria, lacking a signal peptide and a transmembrane structure. Phylogenetic tree analysis revealed that GeCYP714A1 was most closely related to the DcCYP714C2(PKU78454.1) protein from Dendrobium candidum, with a sequence identity of 67.25%. The qRT-PCR analysis of the expression patterns of the GeCYP714A1 gene indicated that GeCYP714A1 had the highest transcription level in G. elata tuber, followed by stem and inflorescence. The study represented that Tis108 inhibited the transcription level of GeCYP714A1 involved in GA deactivation in G. elata tuber, thereby increasing the accumulation of GA and affecting the growth of G. elata tuber. These results provided a basis for further studies of strigolactone regulation of GA signal and tuber development in G. elata.

RevDate: 2024-10-06
CmpDate: 2024-10-06

Yong Y, Hu S, Zhong M, et al (2024)

Horizontal gene transfer from chloroplast to mitochondria of seagrasses in the yellow-Bohai seas.

Genomics, 116(5):110940.

Seagrasses are ideal for studying plant adaptation to marine environments. In this study, the mitochondrial (mt) and chloroplast (cp) genomes of Ruppia sinensis were sequenced. The results showed an extensive gene loss in seagrasses, including a complete loss of cp-rpl19 genes in Zosteraceae, most cp-ndh genes in Hydrocharitaceae, and mt-rpl and mt-rps genes in all seagrasses, except for the mt-rpl16 gene in Phyllospadix iwatensis. Notably, most ribosomal protein genes were lost in the mt and cp genomes. The deleted cp genes were not transferred to the mt genomes through horizontal gene transfer. Additionally, a significant DNA transfer between seagrass organelles was found, with the mt genomes of Zostera containing numerous sequences from the cp genome. Rearrangement analyses revealed an unreported inversion of the cp genome in R. sinensis. Moreover, four positively selected genes (atp8, nad5, atp4, and ccmFn) and five variable regions (matR, atp4, atp8, rps7, and ccmFn) were identified.

RevDate: 2024-09-23
CmpDate: 2024-09-19

Gitschlag BL, Pereira CV, Held JP, et al (2024)

Multiple distinct evolutionary mechanisms govern the dynamics of selfish mitochondrial genomes in Caenorhabditis elegans.

Nature communications, 15(1):8237.

Cells possess multiple mitochondrial DNA (mtDNA) copies, which undergo semi-autonomous replication and stochastic inheritance. This enables mutant mtDNA variants to arise and selfishly compete with cooperative (wildtype) mtDNA. Selfish mitochondrial genomes are subject to selection at different levels: they compete against wildtype mtDNA directly within hosts and indirectly through organism-level selection. However, determining the relative contributions of selection at different levels has proven challenging. We overcome this challenge by combining mathematical modeling with experiments designed to isolate the levels of selection. Applying this approach to many selfish mitochondrial genotypes in Caenorhabditis elegans reveals an unexpected diversity of evolutionary mechanisms. Some mutant genomes persist at high frequency for many generations, despite a host fitness cost, by aggressively outcompeting cooperative genomes within hosts. Conversely, some mutant genomes persist by evading inter-organismal selection. Strikingly, the mutant genomes vary dramatically in their susceptibility to genetic drift. Although different mechanisms can cause high frequency of selfish mtDNA, we show how they give rise to characteristically different distributions of mutant frequency among individuals. Given that heteroplasmic frequency represents a key determinant of phenotypic severity, this work outlines an evolutionary theoretic framework for predicting the distribution of phenotypic consequences among individuals carrying a selfish mitochondrial genome.

RevDate: 2024-09-21
CmpDate: 2024-09-18

Karl MT, Kim YD, Rajendran K, et al (2024)

Invariance of Mitochondria and Synapses in the Primary Visual Cortex of Mammals Provides Insight Into Energetics and Function.

The Journal of comparative neurology, 532(9):e25669.

The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, the organelles responsible for generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features. Notably, we observed an average of 1.9 mitochondria per synapse across mammalian species. When considered together with the trend of decreasing neuron density with larger brain size, we find that brain enlargement in mammals is characterized by increasing proportions of synapses and mitochondria per cortical neuron. These results shed light on the adaptive mechanisms and metabolic dynamics that govern cortical ultrastructure across mammals.

RevDate: 2024-11-05
CmpDate: 2024-11-04

Brunetta HS, Jung AS, Valdivieso-Rivera F, et al (2024)

IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.

The EMBO journal, 43(21):4870-4891.

While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.

RevDate: 2024-09-16

Golubenko MV, VP Puzyrev (2024)

Liberties of the genome: insertions of mitochondrial DNA fragments into nuclear genome.

Vavilovskii zhurnal genetiki i selektsii, 28(5):467-475.

The transition of detached fragments of mitochondrial DNA into the nucleus and their integration into chromosomal DNA is a special kind of genetic variability that highlights the relation between the two genomes and their interaction in a eukaryotic cell. The human genome contains several hundreds of insertions of mtDNA fragments (NUMTS). This paper presents an overview of the current state of research in this area. To date, evidence has been obtained that the occurrence of new mtDNA insertions in the nuclear genome is a seldom but not exceptionally rare event. The integration of new mtDNA fragments into the nuclear genome occurs during double-strand DNA break repair through the non-homologous end joining mechanism. Along with evolutionarily stable "genetic fossils" that were integrated into the nuclear genome millions of years ago and are shared by many species, there are NUMTS that could be species-specific, polymorphic in a species, or "private". Partial copies of mitochondrial DNA in the human nuclear genome can interfere with mtDNA during experimental studies of the mitochondrial genome, such as genotyping, heteroplasmy assessment, mtDNA methylation analysis, and mtDNA copy number estimation. In some cases, the insertion of multiple copies of the complete mitochondrial genome sequence may mimic paternal inheritance of mtDNA. The functional significance of NUMTS is poorly understood. For instance, they may be a source of variability for expression and splicing modulation. The role of NUMTS as a cause of hereditary diseases is negligible, since only a few cases of diseases caused by NUMTS have been described so far. In addition, NUMTS can serve as markers for evolutionary genetic studies. Of particular interest is the meaning of NUMTS in eukaryotic genome evolution. The constant flow of functionally inactive DNA sequences from mitochondria into the nucleus and its significance could be studied in view of the modern concepts of evolutionary theory suggesting non-adaptive complexity and the key role of stochastic processes in the formation of genomic structure.

RevDate: 2024-09-26
CmpDate: 2024-09-24

Zang C, Wang X, Liu Y, et al (2024)

Wolbachia and mosquitoes: Exploring transmission modes and coevolutionary dynamics in Shandong Province, China.

PLoS neglected tropical diseases, 18(9):e0011944.

Vector-borne diseases leave a large footprint on global health. Notable culprits include West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and Japanese encephalitis virus (JEV), all transmitted by Culex mosquitoes. Chemical insecticides have been widely used to reduce the spread of mosquito-borne diseases. Still, mosquitoes are becoming more and more resistant to most chemical insecticides which cause particular harm to the ecology. Wolbachia belongs to the family Ehrlichiaceae in the order Rickettsiales and is a matrilineally inherited endosymbiont present in 60% of insects in nature. Wolbachia is capable of inducing a wide range of reproductive abnormalities in its hosts, such as cytoplasmic incompatibility, and can alter mosquito resistance to pathogen infection. Wolbachia has been proposed as a biological alternative to chemical vector control, and specific research progress and effectiveness have been achieved. Despite the importance of Wolbachia, this strategy has not been tested in Culex pipiens pallens, the most prevalent mosquito species in Shandong Province, China. Little is known about how the mass release of Wolbachia-infected mosquitoes may impact the genetic structure of Culex pipiens pallens, and how the symbiotic bacterium Wolbachia interacts with mitochondria during host mosquito transmission. Based on the population genetic structure of Culex pipiens pallens in Shandong Province, this study investigated the infection rate and infection type of Wolbachia in Shandong Province and jointly analysed the evolutionary relationship between the host mosquito and the symbiotic bacterium Wolbachia. Our study showed that Wolbachia naturally infected by Culex pipiens pallens in Shandong Province was less homologous to Wolbachia infected by Aedes albopictus released from mosquito factory in Guangzhou. Our results also show that Culex pipiens pallens is undergoing demographic expansion in Shandong Province. The overall Wolbachia infection rate of Culex pipiens pallens was 92.8%, and a total of 15 WSP haplotypes were detected. We found that the genetic diversity of Wolbachia was low in Culex pipiens pallens from Shandong Province, and the mosquitoes were infected only with type B Wolbachia. Visualizing the relationship between Culex pipiens pallens and Wolbachia using a tanglegram revealed patterns of widespread associations. A specific coevolutionary relationship exists between the host mosquito and Wolbachia. Knowledge of this mosquito-Wolbachia relationship will provide essential scientific information required for Wolbachia-based vector control approaches in Shandong Province and will lead to a better understanding of the diversity and evolution of Wolbachia for its utility as a biocontrol agent.

RevDate: 2024-10-04
CmpDate: 2024-09-11

Vosseberg J, van Hooff JJE, Köstlbacher S, et al (2024)

The emerging view on the origin and early evolution of eukaryotic cells.

Nature, 633(8029):295-305.

The origin of the eukaryotic cell, with its compartmentalized nature and generally large size compared with bacterial and archaeal cells, represents a cornerstone event in the evolution of complex life on Earth. In a process referred to as eukaryogenesis, the eukaryotic cell is believed to have evolved between approximately 1.8 and 2.7 billion years ago from its archaeal ancestors, with a symbiosis with a bacterial (proto-mitochondrial) partner being a key event. In the tree of life, the branch separating the first from the last common ancestor of all eukaryotes is long and lacks evolutionary intermediates. As a result, the timing and driving forces of the emergence of complex eukaryotic features remain poorly understood. During the past decade, environmental and comparative genomic studies have revealed vital details about the identity and nature of the host cell and the proto-mitochondrial endosymbiont, enabling a critical reappraisal of hypotheses underlying the symbiotic origin of the eukaryotic cell. Here we outline our current understanding of the key players and events underlying the emergence of cellular complexity during the prokaryote-to-eukaryote transition and discuss potential avenues of future research that might provide new insights into the enigmatic origin of the eukaryotic cell.

RevDate: 2024-09-12

Thoral E, Dawson NJ, Bettinazzi S, et al (2024)

An evolving roadmap: using mitochondrial physiology to help guide conservation efforts.

Conservation physiology, 12(1):coae063.

The crucial role of aerobic energy production in sustaining eukaryotic life positions mitochondrial processes as key determinants of an animal's ability to withstand unpredictable environments. The advent of new techniques facilitating the measurement of mitochondrial function offers an increasingly promising tool for conservation approaches. Herein, we synthesize the current knowledge on the links between mitochondrial bioenergetics, ecophysiology and local adaptation, expanding them to the wider conservation physiology field. We discuss recent findings linking cellular bioenergetics to whole-animal fitness, in the current context of climate change. We summarize topics, questions, methods, pitfalls and caveats to help provide a comprehensive roadmap for studying mitochondria from a conservation perspective. Our overall aim is to help guide conservation in natural populations, outlining the methods and techniques that could be most useful to assess mitochondrial function in the field.

RevDate: 2024-10-06
CmpDate: 2024-10-06

Liu GH, Zuo YW, Shan Y, et al (2024)

Structural analysis of the mitochondrial genome of Santalum album reveals a complex branched configuration.

Genomics, 116(5):110935.

BACKGROUND: Santalum album L. is an evergreen tree which is mainly distributes throughout tropical and temperate regions. And it has a great medicinal and economic value.

RESULTS: In this study, the complete mitochondrial genome of S. album were assembled and annotated, which could be descried by a complex branched structure consisting of three contigs. The lengths of these three contigs are 165,122 bp, 93,430 bp and 92,491 bp. We annotated 34 genes coding for proteins (PCGs), 26 tRNA genes, and 4 rRNA genes. The analysis of repeated elements shows that there are 89 SSRs and 242 pairs of dispersed repeats in S. album mitochondrial genome. Also we found 20 MTPTs among the chloroplast and mitochondria. The 20 MTPTs sequences span a combined length of 22,353 bp, making up 15.52 % of the plastome, 6.37 % of the mitochondrial genome. Additionally, by using the Deepred-mt tool, we found 628 RNA editing sites in 34 PCGs. Moreover, significant genomic rearrangement is observed between S. album and its associated mitochondrial genomes. Finally, based on mitochondrial genome PCGs, we deduced the phylogenetic ties between S. album and other angiosperms.

CONCLUSIONS: We reported the mitochondrial genome from Santalales for the first time, which provides a crucial genetic resource for our study of the evolution of mitochondrial genome.

RevDate: 2024-09-07
CmpDate: 2024-09-05

Ou T, Wu Z, Tian C, et al (2024)

Complete mitochondrial genome of Agropyron cristatum reveals gene transfer and RNA editing events.

BMC plant biology, 24(1):830.

BACKGROUND: As an important forage in arid and semi-arid regions, Agropyron cristatum provides livestock with exceptionally high nutritional value. Additionally, A. cristatum exhibits outstanding genetic characteristics to endure drought and disease. Therefore, rich genetic diversity serves as a cornerstone for the improvement of major food crops. The purposes of this study were to systematically describe mitogenome of A.cristatum and preliminarily analyze its internal variations.

RESULT: The A. cristatum mitogenome was a single-ring molecular structure of 381,065 bp that comprised 52 genes, including 35 protein-coding, 3 rRNA and 14 tRNA genes. Among these, two pseudoprotein-coding genes and multiple copies of tRNA genes were observed. A total of 320 repetitive sequences was found to cover more than 10% of the mitogenome (105 simple sequences, 185 dispersed and 30 tandem repeats), which led to a large number of fragment rearrangements in the mitogenome of A. cristatum. Leucine was the most frequent amino acid (n = 1087,10.8%) in the protein-coding genes of A. cristatum mitogenome, and the highest usage codon was ATG (initiation codon). The number of A/T changes at the third base of the codon was much higher than that of G/C. Among 23 PCGs, the range of Pi values is from 0.0021 to 0.0539, with an average of 0.013. Additionally, 81 RNA editing sites were predicted, which were considerably fewer than those reported in other plant mitogenomes. Most of the RNA editing site base positions were concentrated at the first and second codon bases, which were C to T transitions. Moreover, we identified 95 sequence fragments (total length of 34, 343 bp) that were transferred from the chloroplast to mitochondria genes, introns, and intergenic regions. The stability of the tRNA genes was maintained during this process. Selection pressure analysis of 23 protein-coding genes shared by 15 Poaceae plants, showed that most genes were subjected to purifying selection during evolution, whereas rps4, cob, mttB, and ccmB underwent positive selection in different plants. Finally, a phylogenetic tree was constructed based on 22 plant mitogenomes, which showed that Agropyron plants have a high degree of independent heritability in Triticeae.

CONCLUSION: The findings of this study provide new data for a better understanding of A. cristatum genes, and demonstrate that mitogenomes are suitable for the study of plant classifications, such as those of Agropyron. Moreover, it provides a reference for further exploration of the phylogenetic relationships within Agropyron species, and establishes a theoretical basis for the subsequent development and utilization of A. cristatum plant germplasm resources.

RevDate: 2024-10-06
CmpDate: 2024-10-04

Duan X, Shi X, Zhang P, et al (2024)

Identification of concurrent infection with Jaagsiekte sheep retrovirus and maedi-visna virus in China.

Journal of veterinary science, 25(5):e61.

IMPORTANCE: Ovine pulmonary adenomatosis (OPA) and maedi-visna disease (MVD) are chronic and progressive infectious diseases in sheep caused by Jaagsiekte sheep retrovirus (JSRV) and maedi-visna virus (MVV), respectively.

OBJECTIVE: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China.

METHODS: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022.

RESULTS: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464).

CONCLUSIONS AND RELEVANCE: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.

RevDate: 2024-09-06
CmpDate: 2024-09-03

Amaya Romero JE, Chenal C, Ben Chehida Y, et al (2024)

Mitochondrial Variation in Anopheles gambiae and Anopheles coluzzii: Phylogeographic Legacy and Mitonuclear Associations With Metabolic Resistance to Pathogens and Insecticides.

Genome biology and evolution, 16(9):.

Mitochondrial DNA has been a popular marker in phylogeography, phylogeny, and molecular ecology, but its complex evolution is increasingly recognized. Here, we investigated mitochondrial DNA variation in Anopheles gambiae and Anopheles coluzzii, in relation to other species in the Anopheles gambiae complex, by assembling the mitogenomes of 1,219 mosquitoes across Africa. The mitochondrial DNA phylogeny of the Anopheles gambiae complex was consistent with previously reported highly reticulated evolutionary history, revealing important discordances with the species tree. The three most widespread species (An. gambiae, An. coluzzii, and Anopheles arabiensis), known for extensive historical introgression, could not be discriminated based on mitogenomes. Furthermore, a monophyletic clustering of the three saltwater-tolerant species (Anopheles merus, Anopheles melas, and Anopheles bwambae) in the Anopheles gambiae complex also suggested that introgression and possibly selection shaped mitochondrial DNA evolution. Mitochondrial DNA variation in An. gambiae and An. coluzzii across Africa revealed significant partitioning among populations and species. A peculiar mitochondrial DNA lineage found predominantly in An. coluzzii and in the hybrid taxon of the African "far-west" exhibited divergence comparable to the interspecies divergence in the Anopheles gambiae complex, with a geographic distribution matching closely An. coluzzii's geographic range. This phylogeographic relict of the An. coluzzii and An. gambiae split was associated with population and species structure, but not with the rare Wolbachia occurrence. The lineage was significantly associated with single nucleotide polymorphisms in the nuclear genome, particularly in genes associated with pathogen and insecticide resistance. These findings underline potential mitonuclear coevolution history and the role played by mitochondria in shaping metabolic responses to pathogens and insecticides in Anopheles.

RevDate: 2024-09-19
CmpDate: 2024-09-17

de Ree V, Nath TC, Barua P, et al (2024)

Genomic analysis of Strongyloides stercoralis and Strongyloides fuelleborni in Bangladesh.

PLoS neglected tropical diseases, 18(9):e0012440.

BACKGROUND: About 600 million people are estimated to be infected with Strongyloides stercoralis, the species that causes most of the human strongyloidiasis cases. S. stercoralis can also infect non-human primates (NHPs), dogs and cats, rendering these animals putative sources for zoonotic human S. stercoralis infection. S. fuelleborni is normally found in old world NHPs but occasionally also infects humans, mainly in Africa. Dogs in southeast Asia carry at least two types of Strongyloides, only one of which appears to be shared with humans ("dog only" and "human and dog" types). For S. stercoralis with molecular taxonomic information, there is a strong sampling bias towards southeast and east Asia and Australia.

In order to extend the geographic range of sampling, we collected human and dog derived Strongyloides spp. and hookworms from two locations in Bangladesh and subjected them to molecular taxonomic and genomic analysis based on nuclear and mitochondrial sequences. All hookworms found were Necator americanus. Contrary to earlier studies in Asia, we noticed a rather high incidence of S. fuelleborni in humans. Also in this study, we found the two types of S. stercoralis and no indication for genetic isolation from the southeast Asian populations. However, we found one genomically "dog only" type S. stercoralis in a human sample and we found two worms in a dog sample that had a nuclear genome of the "dog only" but a mitochondrial genome of the "human and dog" type.

CONCLUSIONS/SIGNIFICANCE: S. fuelleborni may play a more prominent role as a human parasite in certain places in Asia than previously thought. The introgression of a mitochondria haplotype into the "dog only" population suggests that rare interbreeding between the two S. stercoralis types does occur and that exchange of genetic properties, for example a drug resistance, between the two types is conceivable.

RevDate: 2024-09-12
CmpDate: 2024-09-02

Santos YS, Vidal AH, Abreu EFM, et al (2024)

Detection and molecular characterization of a novel mitovirus associated with Passiflora edulis Sims.

Archives of virology, 169(9):190.

Mitoviruses are cryptic capsidless viruses belonging to the family Mitoviridae that replicate and are maintained in the mitochondria of fungi. Complete mitovirus-like sequences were recently assembled from plant transcriptome data and plant leaf tissue samples. Passion fruit (Passiflora spp.) is an economically important crop for numerous tropical and subtropical countries worldwide, and many virus-induced diseases impact its production. From a large-scale genomic study targeting viruses infecting Passiflora spp. in Brazil, we detected a de novo-assembled contig with similarity to other plant-associated mitoviruses. The contig is ∼2.6 kb long, with a single open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRP). This contig has been named "passion fruit mitovirus-like 1" (PfMv1). An alignment of the predicted amino acid sequence of the RdRP of PfMv1 and those of other plant-associated mitoviruses revealed the presence of the six conserved motifs of mitovirus RdRPs. PfMv1 has 79% coverage and 50.14% identity to Humulus lupulus mitovirus 1. Phylogenetic analysis showed that PfMV1 clustered with other plant-associated mitoviruses in the genus Duamitovirus. Using RT-PCR, we detected a PfMv1-derived fragment, but no corresponding DNA was identified, thus excluding the possibility that this is an endogenized viral-like sequence. This is the first evidence of a replicating mitovirus associated with Passiflora edulis, and it should be classified as a member of a new species, for which we propose the name "Duamitovirus passiflorae".

RevDate: 2024-09-10
CmpDate: 2024-09-10

Chen X, Sun W, Song Y, et al (2024)

Acute waterborne cadmium exposure induces liver ferroptosis in Channa argus.

Ecotoxicology and environmental safety, 283:116947.

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe[2+], ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

RevDate: 2024-09-03
CmpDate: 2024-08-29

Wu H, Qi S, Fan S, et al (2024)

Analysis of the Mitochondrial COI Gene and Genetic Diversity of Endangered Goose Breeds.

Genes, 15(8):.

The mitochondrial cytochrome c oxidase subunit I (COI) genes of six endangered goose breeds (Xupu, Yangjiang, Yan, Wuzong, Baizi, and Lingxian) were sequenced and compared to assess the genetic diversity of endangered goose breeds. By constructing phylogenetic trees and evolutionary maps of genetic relationships, the affinities and degrees of genetic variations among the six different breeds were revealed. A total of 92 polymorphic sites were detected in the 741 bp sequence of the mtDNA COI gene after shear correction, and the GC content of the processed sequence (51.11%) was higher than that of the AT content (48.89%). The polymorphic loci within the populations of five of the six breeds (Xupu, Yangjiang, Yan, Baizi, and Lingxian) were more than 10, the haplotype diversity > 0.5, and the nucleotide diversity (Pi) > 0.005, with the Baizi geese being the exception. A total of 35 haplotypes were detected based on nucleotide variation among sequences, and the goose breed haplotypes showed a central star-shaped dispersion; the FST values were -0.03781 to 0.02645, The greatest genetic differentiation (FST = 0.02645) was observed in Yan and Wuzong breeds. The most frequent genetic exchange (Nm > 15.00) was between the Wuzong and Yangjiang geese. An analysis of molecular variance showed that the population genetic variation mainly came from within the population; the base mismatch differential distribution analysis of the goose breeds and the Tajima's D and Fu's Fs neutral detection of the historical occurrence dynamics of their populations were negative (p > 0.10). The distribution curve of the base mismatches showed a multimodal peak, which indicated that the population tended to be stabilised. These results provide important genetic information for the conservation and management of endangered goose breeds and a scientific basis for the development of effective conservation strategies.

RevDate: 2024-09-03
CmpDate: 2024-08-29

Li H, Liang T, Liu Y, et al (2024)

Exploring Mitochondrial Heterogeneity and Evolutionary Dynamics in Thelephora ganbajun through Population Genomics.

International journal of molecular sciences, 25(16):.

Limited exploration in fungal mitochondrial genetics has uncovered diverse inheritance modes. The mitochondrial genomes are inherited uniparentally in the majority of sexual eukaryotes, our discovery of persistent mitochondrial heterogeneity within the natural population of the basidiomycete fungus Thelephora ganbajun represents a significant advance in understanding mitochondrial inheritance and evolution in eukaryotes. Here, we present a comprehensive analysis by sequencing and assembling the complete mitogenomes of 40 samples exhibiting diverse cox1 heterogeneity patterns from various geographical origins. Additionally, we identified heterogeneous variants in the nad5 gene, which, similar to cox1, displayed variability across multiple copies. Notably, our study reveals a distinct prevalence of introns and homing endonucleases in these heterogeneous genes. Furthermore, we detected potential instances of horizontal gene transfer involving homing endonucleases. Population genomic analyses underscore regional variations in mitochondrial genome composition among natural samples exhibiting heterogeneity. Thus, polymorphisms in heterogeneous genes, introns, and homing endonucleases significantly influence mitochondrial structure, structural variation, and evolutionary dynamics in this species. This study contributes valuable insights into mitochondrial genome architecture, population dynamics, and the evolutionary implications of mitochondrial heterogeneity in sexual eukaryotes.

RevDate: 2024-09-03
CmpDate: 2024-08-29

Wang X, Wang D, Zhang R, et al (2024)

Morphological Structure Identification, Comparative Mitochondrial Genomics and Population Genetic Analysis toward Exploring Interspecific Variations and Phylogenetic Implications of Malus baccata 'ZA' and Other Species.

Biomolecules, 14(8):.

Malus baccata, a valuable germplasm resource in the genus Malus, is indigenous to China and widely distributed. However, little is known about the lineage composition and genetic basis of 'ZA', a mutant type of M. baccata. In this study, we compared the differences between 'ZA' and wild type from the perspective of morphology and ultrastructure and analyzed their chloroplast pigment content based on biochemical methods. Further, the complete mitogenome of M. baccata 'ZA' was assembled and obtained by next-generation sequencing. Subsequently, its molecular characteristics were analyzed using Geneious, MISA-web, and CodonW toolkits. Furthermore, by examining 106 Malus germplasms and 42 Rosaceae species, we deduced and elucidated the evolutionary position of M. baccata 'ZA', as well as interspecific variations among different individuals. In comparison, the total length of the 'ZA' mitogenome (GC content: 45.4%) is 374,023 bp, which is approximately 2.33 times larger than the size (160,202 bp) of the plastome (GC: 36.5%). The collinear analysis results revealed abundant repeats and genome rearrangements occurring between different Malus species. Additionally, we identified 14 plastid-driven fragment transfer events. A total of 54 genes have been annotated in the 'ZA' mitogenome, including 35 protein-coding genes, 16 tRNAs, and three rRNAs. By calculating nucleotide polymorphisms and selection pressure for 24 shared core mitochondrial CDSs from 42 Rosaceae species (including 'ZA'), we observed that the nad3 gene exhibited minimal variation, while nad4L appeared to be evolving rapidly. Population genetics analysis detected a total of 1578 high-quality variants (1424 SNPs, 60 insertions, and 94 deletions; variation rate: 1/237) among samples from 106 Malus individuals. Furthermore, by constructing phylogenetic trees based on both Malus and Rosaceae taxa datasets, it was preliminarily demonstrated that 'ZA' is closely related to M. baccata, M. sieversii, and other proximate species in terms of evolution. The sequencing data obtained in this study, along with our findings, contribute to expanding the mitogenomic resources available for Rosaceae research. They also hold reference significance for molecular identification studies as well as conservation and breeding efforts focused on excellent germplasms.

RevDate: 2024-09-01

Tian L, Luo Y, Ren J, et al (2024)

The Role of Oxidative Stress in Hypomagnetic Field Effects.

Antioxidants (Basel, Switzerland), 13(8):.

The geomagnetic field (GMF) is crucial for the survival and evolution of life on Earth. The weakening of the GMF, known as the hypomagnetic field (HMF), significantly affects various aspects of life on Earth. HMF has become a potential health risk for future deep space exploration. Oxidative stress is directly involved in the biological effects of HMF on animals or cells. Oxidative stress occurs when there is an imbalance favoring oxidants over antioxidants, resulting in cellular damage. Oxidative stress is a double-edged sword, depending on the degree of deviation from homeostasis. In this review, we summarize the important experimental findings from animal and cell studies on HMF exposure affecting intracellular reactive oxygen species (ROS), as well as the accompanying many physiological abnormalities, such as cognitive dysfunction, the imbalance of gut microbiota homeostasis, mood disorders, and osteoporosis. We discuss new insights into the molecular mechanisms underlying these HMF effects in the context of the signaling pathways related to ROS. Among them, mitochondria are considered to be the main organelles that respond to HMF-induced stress by regulating metabolism and ROS production in cells. In order to unravel the molecular mechanisms of HMF action, future studies need to consider the upstream and downstream pathways associated with ROS.

RevDate: 2024-10-07
CmpDate: 2024-08-28

Bhattacharya M, Bhowmik D, Q Yin (2025)

In Vitro Cleavage Assay to Characterize DENV NS2B3 Antagonism of cGAS.

Methods in molecular biology (Clifton, N.J.), 2854:153-170.

cGAS is a key cytosolic dsDNA receptor that senses viral infection and elicits interferon production through the cGAS-cGAMP-STING axis. cGAS is activated by dsDNA from viral and bacterial origins as well as dsDNA leaked from damaged mitochondria and nucleus. Eventually, cGAS activation launches the cell into an antiviral state to restrict the replication of both DNA and RNA viruses. Throughout the long co-evolution, viruses devise many strategies to evade cGAS detection or suppress cGAS activation. We recently reported that the Dengue virus protease NS2B3 proteolytically cleaves human cGAS in its N-terminal region, effectively reducing cGAS binding to DNA and consequent production of the second messenger cGAMP. Several other RNA viruses likely adopt the cleavage strategy. Here, we describe a protocol for the purification of recombinant human cGAS and Dengue NS2B3 protease, as well as the in vitro cleavage assay.

RevDate: 2024-08-26
CmpDate: 2024-08-23

Guo Y, Wen H, Chen Z, et al (2024)

Conjoint analysis of succinylome and phosphorylome reveals imbalanced HDAC phosphorylation-driven succinylayion dynamic contibutes to lung cancer.

Briefings in bioinformatics, 25(5):.

Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming.

RevDate: 2024-08-23
CmpDate: 2024-08-20

García-Merchán VH, Palero F, Rufino M, et al (2024)

Mitochondrial, nuclear and morphological differentiation in the swimming crab Liocarcinus depurator along the Atlantic-Mediterranean transition.

Scientific reports, 14(1):19342.

Environmental gradients in the sea may coincide with phenotypic or genetic gradients resulting from an evolutionary balance between selection and dispersal. The population differentiation of the swimming crab, Liocarcinus depurator, an important by-catch species in the Mediterranean Sea and North-East Atlantic, was assessed using both genetic and morphometric approaches. A total of 472 specimens were collected along its distribution area, and 17 morphometric landmarks, one mitochondrial gene (COI) and 11 polymorphic microsatellite markers were scored in 350, 287 and 280 individuals, respectively. Morphometric data lacked significant differences, but genetic analyses showed significant genetic differentiation between Atlantic and Mediterranean populations, with a steeper gradient in COI compared to microsatellite markers. Interestingly, nuclear differentiation was due to an outlier locus with a gradient in the Atlantic-Mediterranean transition area overlapping with the mtDNA gradient. Such overlapping clines are likely to be maintained by natural selection. Our results suggest a scenario of past isolation with local adaptation and secondary contact between the two basins. Local adaptation during the process of vicariance may reinforce genetic differentiation at loci maintained by environmental selection even after secondary contact.

RevDate: 2024-09-10

Sizek H, Deritei D, Fleig K, et al (2024)

Unlocking mitochondrial dysfunction-associated senescence (MiDAS) with NAD[+] - A Boolean model of mitochondrial dynamics and cell cycle control.

Translational oncology, 49:102084.

The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress - a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively captures key aspects of mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response to SIRT3 knockdown or oxidative stress. Our model reaffirms the protective role of NAD[+] and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model provides mechanistic insights into the distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and offers a foundation for building multiscale models of tissue aging.

RevDate: 2024-09-12
CmpDate: 2024-09-10

Klirs Y, Novosolov M, Gissi C, et al (2024)

Evolutionary Insights from the Mitochondrial Genome of Oikopleura dioica: Sequencing Challenges, RNA Editing, Gene Transfers to the Nucleus, and tRNA Loss.

Genome biology and evolution, 16(9):.

Sequencing the mitochondrial genome of the tunicate Oikopleura dioica is a challenging task due to the presence of long poly-A/T homopolymer stretches, which impair sequencing and assembly. Here, we report on the sequencing and annotation of the majority of the mitochondrial genome of O. dioica by means of combining several DNA and amplicon reads obtained by Illumina and MinIon Oxford Nanopore Technologies with public RNA sequences. We document extensive RNA editing, since all homopolymer stretches present in the mitochondrial DNA correspond to 6U-regions in the mitochondrial RNA. Out of the 13 canonical protein-coding genes, we were able to detect eight, plus an unassigned open reading frame that lacked sequence similarity to canonical mitochondrial protein-coding genes. We show that the nad3 gene has been transferred to the nucleus and acquired a mitochondria-targeting signal. In addition to two very short rRNAs, we could only identify a single tRNA (tRNA-Met), suggesting multiple losses of tRNA genes, supported by a corresponding loss of mitochondrial aminoacyl-tRNA synthetases in the nuclear genome. Based on the eight canonical protein-coding genes identified, we reconstructed maximum likelihood and Bayesian phylogenetic trees and inferred an extreme evolutionary rate of this mitochondrial genome. The phylogenetic position of appendicularians among tunicates, however, could not be accurately determined.

RevDate: 2024-08-21
CmpDate: 2024-08-19

Bajić V, Schulmann VH, K Nowick (2024)

mtDNA "nomenclutter" and its consequences on the interpretation of genetic data.

BMC ecology and evolution, 24(1):110.

Population-based studies of human mitochondrial genetic diversity often require the classification of mitochondrial DNA (mtDNA) haplotypes into more than 5400 described haplogroups, and further grouping those into hierarchically higher haplogroups. Such secondary haplogroup groupings (e.g., "macro-haplogroups") vary across studies, as they depend on the sample quality, technical factors of haplogroup calling, the aims of the study, and the researchers' understanding of the mtDNA haplogroup nomenclature. Retention of historical nomenclature coupled with a growing number of newly described mtDNA lineages results in increasingly complex and inconsistent nomenclature that does not reflect phylogeny well. This "clutter" leaves room for grouping errors and inconsistencies across scientific publications, especially when the haplogroup names are used as a proxy for secondary groupings, and represents a source for scientific misinterpretation. Here we explore the effects of phylogenetically insensitive secondary mtDNA haplogroup groupings, and the lack of standardized secondary haplogroup groupings on downstream analyses and interpretation of genetic data. We demonstrate that frequency-based analyses produce inconsistent results when different secondary mtDNA groupings are applied, and thus allow for vastly different interpretations of the same genetic data. The lack of guidelines and recommendations on how to choose appropriate secondary haplogroup groupings presents an issue for the interpretation of results, as well as their comparison and reproducibility across studies. To reduce biases originating from arbitrarily defined secondary nomenclature-based groupings, we suggest that future updates of mtDNA phylogenies aimed for the use in mtDNA haplogroup nomenclature should also provide well-defined and standardized sets of phylogenetically meaningful algorithm-based secondary haplogroup groupings such as "macro-haplogroups", "meso-haplogroups", and "micro-haplogroups". Ideally, each of the secondary haplogroup grouping levels should be informative about different human population history events. Those phylogenetically informative levels of haplogroup groupings can be easily defined using TreeCluster, and then implemented into haplogroup callers such as HaploGrep3. This would foster reproducibility across studies, provide a grouping standard for population-based studies, and reduce errors associated with haplogroup nomenclatures in future studies.

RevDate: 2024-08-28
CmpDate: 2024-08-19

Ge J, Li H, Liang X, et al (2024)

SLC30A9: an evolutionarily conserved mitochondrial zinc transporter essential for mammalian early embryonic development.

Cellular and molecular life sciences : CMLS, 81(1):357.

SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.

RevDate: 2024-09-04
CmpDate: 2024-09-04

Zhang Y, Liu S, Mostert D, et al (2024)

Virulence of banana wilt-causing fungal pathogen Fusarium oxysporum tropical race 4 is mediated by nitric oxide biosynthesis and accessory genes.

Nature microbiology, 9(9):2232-2243.

Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most damaging plant diseases known. Foc race 1 (R1) decimated the Gros Michel-based banana (Musa acuminata) trade, and now Foc tropical race 4 (TR4) threatens global production of its replacement, the Cavendish banana. Here population genomics revealed that all Cavendish banana-infecting Foc race 4 strains share an evolutionary origin distinct from that of R1 strains. Although TR4 lacks accessory chromosomes, it contains accessory genes at the ends of some core chromosomes that are enriched for virulence and mitochondria-related functions. Meta-transcriptomics revealed the unique induction of the entire mitochondrion-localized nitric oxide (NO) biosynthesis pathway upon TR4 infection. Empirically, we confirmed the unique induction of a NO burst in TR4, suggesting that nitrosative pressure may contribute to virulence. Targeted mutagenesis demonstrated the functional importance of fungal NO production and the accessory gene SIX4 as virulence factors.

RevDate: 2024-08-29
CmpDate: 2024-08-27

von Känel C, Stettler P, Esposito C, et al (2024)

Pam16 and Pam18 were repurposed during Trypanosoma brucei evolution to regulate the replication of mitochondrial DNA.

PLoS biology, 22(8):e3002449.

Protein import and genome replication are essential processes for mitochondrial biogenesis and propagation. The J-domain proteins Pam16 and Pam18 regulate the presequence translocase of the mitochondrial inner membrane. In the protozoan Trypanosoma brucei, their counterparts are TbPam16 and TbPam18, which are essential for the procyclic form (PCF) of the parasite, though not involved in mitochondrial protein import. Here, we show that during evolution, the 2 proteins have been repurposed to regulate the replication of maxicircles within the intricate kDNA network, the most complex mitochondrial genome known. TbPam18 and TbPam16 have inactive J-domains suggesting a function independent of heat shock proteins. However, their single transmembrane domain is essential for function. Pulldown of TbPam16 identifies a putative client protein, termed MaRF11, the depletion of which causes the selective loss of maxicircles, akin to the effects observed for TbPam18 and TbPam16. Moreover, depletion of the mitochondrial proteasome results in increased levels of MaRF11. Thus, we have discovered a protein complex comprising TbPam18, TbPam16, and MaRF11, that controls maxicircle replication. We propose a working model in which the matrix protein MaRF11 functions downstream of the 2 integral inner membrane proteins TbPam18 and TbPam16. Moreover, we suggest that the levels of MaRF11 are controlled by the mitochondrial proteasome.

RevDate: 2024-08-27
CmpDate: 2024-08-27

Kutzer MAM, Cornish B, Jamieson M, et al (2024)

Mitochondrial background can explain variable costs of immune deployment.

Journal of evolutionary biology, 37(9):1125-1133.

Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here, we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or to a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation in immune-stimulated flies between lifespan and the proportion of time cybrids spent moving while alive. Our results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.

RevDate: 2024-08-15
CmpDate: 2024-08-15

Leung A, Patel R, Chirachon V, et al (2024)

Tribulus (Zygophyllaceae) as a case study for the evolution of C2 and C4 photosynthesis.

Plant, cell & environment, 47(9):3541-3560.

C2 photosynthesis is a photosynthetic pathway in which photorespiratory CO2 release and refixation are enhanced in leaf bundle sheath (BS) tissues. The evolution of C2 photosynthesis has been hypothesized to be a major step in the origin of C4 photosynthesis, highlighting the importance of studying C2 evolution. In this study, physiological, anatomical, ultrastructural, and immunohistochemical properties of leaf photosynthetic tissues were investigated in six non-C4 Tribulus species and four C4 Tribulus species. At 42°C, T. cristatus exhibited a photosynthetic CO2 compensation point in the absence of respiration (C*) of 21 µmol mol[-1], below the C3 mean C* of 73 µmol mol[-1]. Tribulus astrocarpus had a C* value at 42°C of 55 µmol mol[-1], intermediate between the C3 species and the C2 T. cristatus. Glycine decarboxylase (GDC) allocation to BS tissues was associated with lower C*. Tribulus cristatus and T. astrocarpus allocated 86% and 30% of their GDC to the BS tissues, respectively, well above the C3 mean of 11%. Tribulus astrocarpus thus exhibits a weaker C2 (termed sub-C2) phenotype. Increased allocation of mitochondria to the BS and decreased length-to-width ratios of BS cells, were present in non-C4 species, indicating a potential role in C2 and C4 evolution.

RevDate: 2024-09-26
CmpDate: 2024-09-26

Harry CJ, Hibshman JD, Damatac A, et al (2024)

Protocol for fluorescent live-cell staining of tardigrades.

STAR protocols, 5(3):103232.

Tardigrades are microscopic organisms with exceptional resilience to environmental extremes. Most protocols to visualize the internal anatomy of tardigrades rely on fixation, hampering our understanding of dynamic changes to organelles and other subcellular components. Here, we provide protocols for staining live tardigrade adults and other postembryonic stages, facilitating real-time visualization of structures including lipid droplets, mitochondria, lysosomes, and DNA.

RevDate: 2024-09-18
CmpDate: 2024-09-12

Zhang L, Liu ZS, Dong YZ, et al (2024)

Molecular cloning and functional characterization of mitochondrial RNA splicing 2 in fish Megalobrama amblycephala, and its potential roles in magnesium homeostasis and mitochondrial function.

Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 297:111727.

Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg[2+]) channel located in the inner mitochondrial membrane, thereby mediating the Mg[2+] influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg[2+] influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg[2+] influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.

RevDate: 2024-08-12
CmpDate: 2024-08-10

Zhan L, Chen Y, He J, et al (2024)

The Phylogenetic Relationships of Major Lizard Families Using Mitochondrial Genomes and Selection Pressure Analyses in Anguimorpha.

International journal of molecular sciences, 25(15):.

Anguimorpha, within the order Squamata, represents a group with distinct morphological and behavioral characteristics in different ecological niches among lizards. Within Anguimorpha, there is a group characterized by limb loss, occupying lower ecological niches, concentrated within the subfamily Anguinae. Lizards with limbs and those without exhibit distinct locomotor abilities when adapting to their habitats, which in turn necessitate varying degrees of energy expenditure. Mitochondria, known as the metabolic powerhouses of cells, play a crucial role in providing approximately 95% of an organism's energy. Functionally, mitogenomes (mitochondrial genomes) can serve as a valuable tool for investigating potential adaptive evolutionary selection behind limb loss in reptiles. Due to the variation of mitogenome structures among each species, as well as its simple genetic structure, maternal inheritance, and high evolutionary rate, the mitogenome is increasingly utilized to reconstruct phylogenetic relationships of squamate animals. In this study, we sequenced the mitogenomes of two species within Anguimorpha as well as the mitogenomes of two species in Gekkota and four species in Scincoidea. We compared these data with the mitogenome content and evolutionary history of related species. Within Anguimorpha, between the mitogenomes of limbless and limbed lizards, a branch-site model analysis supported the presence of 10 positively selected sites: Cytb protein (at sites 183 and 187), ND2 protein (at sites 90, 155, and 198), ND3 protein (at site 21), ND5 protein (at sites 12 and 267), and ND6 protein (at sites 72 and 119). These findings suggested that positive selection of mitogenome in limbless lizards may be associated with the energy requirements for their locomotion. Additionally, we acquired data from 205 mitogenomes from the NCBI database. Bayesian inference (BI) and Maximum Likelihood (ML) trees were constructed using the 13 mitochondrial protein-coding genes (PCGs) and two rRNAs (12S rRNA and 16S rRNA) from 213 mitogenomes. Our phylogenetic tree and the divergence time estimates for Squamata based on mitogenome data are consistent with results from previous studies. Gekkota was placed at the root of Squamata in both BI and ML trees. However, within the Toxicofera clade, due to long-branch attraction, Anguimorpha and (Pleurodonta + (Serpentes + Acrodonta)) were closely related groupings, which might indicate errors and also demonstrate that mitogenome-based phylogenetic trees may not effectively resolve long-branch attraction issues. Additionally, we reviewed the origin and diversification of Squamata throughout the Mesozoic era, suggesting that Squamata originated in the Late Triassic (206.05 Mya), with the diversification of various superfamilies occurring during the Cretaceous period. Future improvements in constructing squamate phylogenetic relationships using mitogenomes will rely on identifying snake and acrodont species with slower evolutionary rates, ensuring comprehensive taxonomic coverage of squamate diversity, and increasing the number of genes analyzed.

RevDate: 2024-08-14
CmpDate: 2024-08-10

Zhang X, Ding Z, Lou H, et al (2024)

A Systematic Review and Developmental Perspective on Origin of CMS Genes in Crops.

International journal of molecular sciences, 25(15):.

Cytoplasmic male sterility (CMS) arises from the incompatibility between the nucleus and cytoplasm as typical representatives of the chimeric structures in the mitochondrial genome (mitogenome), which has been extensively applied for hybrid seed production in various crops. The frequent occurrence of chimeric mitochondrial genes leading to CMS is consistent with the mitochondrial DNA (mtDNA) evolution. The sequence conservation resulting from faithfully maternal inheritance and the chimeric structure caused by frequent sequence recombination have been defined as two major features of the mitogenome. However, when and how these chimeric mitochondrial genes appear in the context of the highly conserved reproduction of mitochondria is an enigma. This review, therefore, presents the critical view of the research on CMS in plants to elucidate the mechanisms of this phenomenon. Generally, distant hybridization is the main mechanism to generate an original CMS source in natural populations and in breeding. Mitochondria and mitogenomes show pleomorphic and dynamic changes at key stages of the life cycle. The promitochondria in dry seeds develop into fully functioning mitochondria during seed imbibition, followed by massive mitochondria or mitogenome fusion and fission in the germination stage along with changes in the mtDNA structure and quantity. The mitogenome stability is controlled by nuclear loci, such as the nuclear gene Msh1. Its suppression leads to the rearrangement of mtDNA and the production of heritable CMS genes. An abundant recombination of mtDNA is also often found in distant hybrids and somatic/cybrid hybrids. Since mtDNA recombination is ubiquitous in distant hybridization, we put forward a hypothesis that the original CMS genes originated from mtDNA recombination during the germination of the hybrid seeds produced from distant hybridizations to solve the nucleo-cytoplasmic incompatibility resulting from the allogenic nuclear genome during seed germination.

RevDate: 2024-08-12
CmpDate: 2024-08-09

Williams SK, Jerlström Hultqvist J, Eglit Y, et al (2024)

Extreme mitochondrial reduction in a novel group of free-living metamonads.

Nature communications, 15(1):6805.

Metamonads are a diverse group of heterotrophic microbial eukaryotes adapted to living in hypoxic environments. All metamonads but one harbour metabolically altered 'mitochondrion-related organelles' (MROs) with reduced functions, however the degree of reduction varies. Here, we generate high-quality draft genomes, transcriptomes, and predicted proteomes for five recently discovered free-living metamonads. Phylogenomic analyses placed these organisms in a group we name the 'BaSk' (Barthelonids+Skoliomonads) clade, a deeply branching sister group to the Fornicata, a phylum that includes parasitic and free-living flagellates. Bioinformatic analyses of gene models shows that these organisms are predicted to have extremely reduced MRO proteomes in comparison to other free-living metamonads. Loss of the mitochondrial iron-sulfur cluster assembly system in some organisms in this group appears to be linked to the acquisition in their common ancestral lineage of a SUF-like minimal system Fe/S cluster pathway by lateral gene transfer. One of the isolates, Skoliomonas litria, appears to have lost all other known MRO pathways. No proteins were confidently assigned to the predicted MRO proteome of this organism suggesting that the organelle has been lost. The extreme mitochondrial reduction observed within this free-living anaerobic protistan clade demonstrates that mitochondrial functions may be completely lost even in free-living organisms.

RevDate: 2024-08-11
CmpDate: 2024-08-09

Proust B, Herak Bosnar M, Ćetković H, et al (2024)

Mitochondrial NME6: A Paradigm Change within the NME/NDP Kinase Protein Family?.

Cells, 13(15):.

Eukaryotic NMEs/NDP kinases are a family of 10 multifunctional proteins that occur in different cellular compartments and interact with various cellular components (proteins, membranes, and DNA). In contrast to the well-studied Group I NMEs (NME1-4), little is known about the more divergent Group II NMEs (NME5-9). Three recent publications now shed new light on NME6. First, NME6 is a third mitochondrial NME, largely localized in the matrix space, associated with the mitochondrial inner membrane. Second, while its monomeric form is inactive, NME6 gains NDP kinase activity through interaction with mitochondrial RCC1L. This challenges the current notion that mammalian NMEs require the formation of hexamers to become active. The formation of complexes between NME6 and RCC1L, likely heterodimers, seemingly obviates the necessity for hexamer formation, stabilizing a NDP kinase-competent conformation. Third, NME6 is involved in mitochondrial gene maintenance and expression by providing (d)NTPs for replication and transcription (in particular the pyrimidine nucleotides) and by a less characterized mechanism that supports mitoribosome function. This review offers an overview of NME evolution and structure and highlights the new insight into NME6. The new findings position NME6 as the most comprehensively studied protein in NME Group II and may even suggest it as a new paradigm for related family members.

RevDate: 2024-08-10

Zachos KA, Gamboa JA, Dewji AS, et al (2024)

The interplay between mitochondria, the gut microbiome and metabolites and their therapeutic potential in primary mitochondrial disease.

Frontiers in pharmacology, 15:1428242.

The various roles of the mitochondria and the microbiome in health and disease have been thoroughly investigated, though they are often examined independently and in the context of chronic disease. However, the mitochondria and microbiome are closely connected, namely, through their evolution, maternal inheritance patterns, overlapping role in many diseases and their importance in the maintenance of human health. The concept known as the "mitochondria-microbiome crosstalk" is the ongoing bidirectional crosstalk between these two entities and warrants further exploration and consideration, especially in the context of primary mitochondrial disease, where mitochondrial dysfunction can be detrimental for clinical manifestation of disease, and the role and composition of the microbiome is rarely investigated. A potential mechanism underlying this crosstalk is the role of metabolites from both the mitochondria and the microbiome. During digestion, gut microbes modulate compounds found in food, which can produce metabolites with various bioactive effects. Similarly, mitochondrial metabolites are produced from substrates that undergo biochemical processes during cellular respiration. This review aims to provide an overview of current literature examining the mitochondria-microbiome crosstalk, the role of commonly studied metabolites serve in signaling and mediating these biochemical pathways, and the impact diet has on both the mitochondria and the microbiome. As a final point, this review highlights the up-to-date implications of the mitochondria-microbiome crosstalk in mitochondrial disease and its potential as a therapeutic tool or target.

RevDate: 2024-08-16

Wu Y, Liu Y, Feng Y, et al (2024)

Evolution of therapeutic strategy based on oxidant-antioxidant balance for fuchs endothelial corneal dystrophy.

The ocular surface, 34:247-261 pii:S1542-0124(24)00083-1 [Epub ahead of print].

Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.

RevDate: 2024-08-09
CmpDate: 2024-08-07

Raynes Y, Santiago JC, Lemieux FA, et al (2024)

Sex, tissue, and mitochondrial interactions modify the transcriptional response to rapamycin in Drosophila.

BMC genomics, 25(1):766.

BACKGROUND: Many common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies.

RESULTS: We assayed gene expression with and without rapamycin exposure across three distinct body parts (head, thorax, abdomen) of D. melanogaster flies, bearing either their native melanogaster mitochondrial genome or the mitochondrial genome from a related species, D. simulans. The fully factorial RNA-seq study design revealed a large number of genes that responded to the rapamycin treatment in a sex-dependent and tissue-dependent manner, and relatively few genes with the transcriptional response to rapamycin affected by the mitochondrial background. Reanalysis of an earlier study confirmed that mitochondria can have a temporal influence on rapamycin response.

CONCLUSIONS: We found significant and wide-ranging effects of sex and body part, alongside a subtle, potentially time-dependent, influence of mitochondria on the transcriptional response to rapamycin. Our findings suggest a number of pathways that could be crucial for predicting potential side effects of mTOR inhibition in a particular sex or tissue. Further studies of the temporal response to rapamycin are necessary to elucidate the effects of the mitochondrial background on mTOR and its inhibition.

RevDate: 2024-08-28
CmpDate: 2024-08-05

Veeraragavan S, Johansen M, IG Johnston (2024)

Evolution and maintenance of mtDNA gene content across eukaryotes.

The Biochemical journal, 481(15):1015-1042.

Across eukaryotes, most genes required for mitochondrial function have been transferred to, or otherwise acquired by, the nucleus. Encoding genes in the nucleus has many advantages. So why do mitochondria retain any genes at all? Why does the set of mtDNA genes vary so much across different species? And how do species maintain functionality in the mtDNA genes they do retain? In this review, we will discuss some possible answers to these questions, attempting a broad perspective across eukaryotes. We hope to cover some interesting features which may be less familiar from the perspective of particular species, including the ubiquity of recombination outside bilaterian animals, encrypted chainmail-like mtDNA, single genes split over multiple mtDNA chromosomes, triparental inheritance, gene transfer by grafting, gain of mtDNA recombination factors, social networks of mitochondria, and the role of mtDNA dysfunction in feeding the world. We will discuss a unifying picture where organismal ecology and gene-specific features together influence whether organism X retains mtDNA gene Y, and where ecology and development together determine which strategies, importantly including recombination, are used to maintain the mtDNA genes that are retained.

RevDate: 2024-08-30
CmpDate: 2024-08-30

Zhang Y, Liu J, Zheng R, et al (2024)

Curcumin analogue EF24 prevents alveolar epithelial cell senescence to ameliorate idiopathic pulmonary fibrosis via activation of PTEN.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 133:155882.

BACKGROUND: Treating Idiopathic pulmonary fibrosis (IPF) remains challenging owing to its relentless progression, grim prognosis, and the scarcity of effective treatment options. Emerging evidence strongly supports the critical role of accelerated senescence in alveolar epithelial cells (AECs) in driving the progression of IPF. Consequently, targeting senescent AECs emerges as a promising therapeutic strategy for IPF.

PURPOSE: Curcumin analogue EF24 is a derivative of curcumin and shows heightened bioactivity encompassing anti-inflammatory, anti-tumor and anti-aging properties. The objective of this study was to elucidate the therapeutic potential and underlying molecular mechanisms of EF24 in the treatment of IPF.

METHODS: A549 and ATII cells were induced to become senescent using bleomycin. Senescence markers were examined using different methods including senescence-associated β-galactosidase (SA-β-gal) staining, western blotting, and q-PCR. Mice were intratracheally administrated with bleomycin to induce pulmonary fibrosis. This was validated by micro-computed tomography (CT), masson trichrome staining, and transmission electron microscope (TEM). The role and underlying mechanisms of EF24 in IPF were determined in vitro and in vivo by evaluating the expressions of PTEN, AKT/mTOR/NF-κB signaling pathway, and mitophagy using western blotting or flow cytometry.

RESULTS: We identified that the curcumin analogue EF24 was the most promising candidate among 12 compounds against IPF. EF24 treatment significantly reduced senescence biomarkers in bleomycin-induced senescent AECs, including SA-β-Gal, PAI-1, P21, and the senescence-associated secretory phenotype (SASP). EF24 also effectively inhibited fibroblast activation which was induced by senescent AECs or TGF-β. We revealed that PTEN activation was integral for EF24 to inhibit AECs senescence by suppressing the AKT/mTOR/NF-κB signaling pathway. Additionally, EF24 improved mitochondrial dysfunction through induction of mitophagy. Furthermore, EF24 administration significantly reduced the senescent phenotype induced by bleomycin in the lung tissues of mice. Notably, EF24 mitigates fibrosis and promotes overall health benefits in both the acute and chronic phases of IPF, suggesting its therapeutic potential in IPF treatment.

CONCLUSION: These findings collectively highlight EF24 as a new and effective therapeutic agent against IPF by inhibiting senescence in AECs.

RevDate: 2024-08-02

Özdemir M, S Dennerlein (2024)

The TOM complex from an evolutionary perspective and the functions of TOMM70.

Biological chemistry [Epub ahead of print].

In humans, up to 1,500 mitochondrial precursor proteins are synthesized at cytosolic ribosomes and must be imported into the organelle. This is not only essential for mitochondrial but also for many cytosolic functions. The majority of mitochondrial precursor proteins are imported over the translocase of the outer membrane (TOM). In recent years, high-resolution structure analyses from different organisms shed light on the composition and arrangement of the TOM complex. Although significant similarities have been found, differences were also observed, which have been favored during evolution and could reflect the manifold functions of TOM with cellular signaling and its response to altered metabolic situations. A key component within these regulatory mechanisms is TOMM70, which is involved in protein import, forms contacts to the ER and the nucleus, but is also involved in cellular defense mechanisms during infections.

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

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Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin and even a collection of poetry — Chicago Poems by Carl Sandburg.

Timelines

ESP now offers a large collection of user-selected side-by-side timelines (e.g., all science vs. all other categories, or arts and culture vs. world history), designed to provide a comparative context for appreciating world events.

Biographies

Biographical information about many key scientists (e.g., Walter Sutton).

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 28 JUL 2024 )