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Mitochondria importance articles
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14 of 176 articles · updated 2026-09-18T14:04Z
- biorxiv2026-08-20score 86immunologymtDNAcomputational
Ancient human mtDNA encrypts antimicrobial peptides; 14 kill bacteria and one works in mouse skin
Mining 2,025 ancient human mitochondrial genomes produced 65 encrypted peptide candidates the authors call mitochondrins. Thirty-eight were synthesized; 14 killed clinically relevant Gram-negative and Gram-positive bacteria. Activity tracked hydrophobic-cationic patterning, not length or charge alone, and one peptide reduced bacterial burden in a murine skin-abscess model.
Source preprint: Ancient human mitochondrial genomes encode antimicrobial peptides
- biorxiv2026-09-03score 81computationalmetabolismOXPHOS
Underpredicted mitochondrial ADP/ATP carrier kcat values, not leaderboard scores, break yeast growth models
Six machine-learning predictors of enzyme turnover number (kcat) are only moderately accurate on a BRENDA-derived set and collapse to R-squared of 0.20 or lower on EnzyExtract, where training-set overlap is thinner. When those predicted kcat values parameterize enzyme-constrained genome-scale models of Saccharomyces cerevisiae, benchmark rank does not predict growth accuracy. The failure localizes to high-leverage mitochondrial ADP/ATP carrier turnover numbers: underpredict them and the model chokes adenine nucleotide exchange and invents a cytosolic ATP shortage.
Source preprint: Beyond benchmark accuracy: machine-learning turnover-number predictors require system-level validation
- biorxiv2026-08-21score 81computationalgeneticsmtDNA
Plant mitochondria keep a compact AOX–NAC stress module; human disease genes pile onto an expanded ISR–mtDNA network
An Arabidopsis-versus-human in silico comparison finds the same mitochondrial stress logic in both kingdoms, but not the same architecture. Plants organize alternative respiration and retrograde signaling as a compact AOX–NAC module. Humans expand integrated-stress-response and mtDNA-maintenance neighborhoods — and those expanded modules are the ones enriched for mitochondrial disease genes.
Source preprint: From Plants to Patients: Mitochondrial Stress Signaling as a Systems Framework for Human Disease Vulnerability
- biorxiv2026-08-08score 78neurobiologyOXPHOSmetabolism
Visual cortex sits on mitochondria-poor tissue; semantic cortex sits on mitochondria-rich tissue
7T fMRI during natural-scene viewing, split by image-to-brain encoding into variance unique to visual versus semantic features, was compared with postmortem mitochondrial atlases under spatial-autocorrelation-preserving inference. Visual-specific cortical variance aligns negatively with mitochondrial density and respiratory capacity. Semantic-specific variance aligns positively with mitochondrial density. Transcriptomic enrichments run in opposite mitochondrial and cellular programs along those two representational axes. How cortex represents the world tracks how the tissue is provisioned with mitochondria.
Source preprint: Distinct mitochondrial phenotypes align with visual and semantic representations across human cortex
- biorxiv2026-09-02score 74mitochondrial dynamicscomputationalstructural biology
PRISM stably paints mitochondria with four other organelles and returns 500-plus contact metrics per cell
A single PiggyBac-integrable cassette (PRISM: Plasmid-based Reporter for Intracellular Spectral Microscopy) stably labels mitochondria, Golgi, peroxisomes, endoplasmic reticulum, and lysosomes for spectral microscopy, then a modular pipeline extracts more than 500 morphology, distribution, pairwise, and higher-order contact metrics per cell. The authors use it to score cytoskeletal perturbation, phosphatidylinositol 4-phosphate redistribution after lysosomal damage, and organelle-network remodeling during Zika virus infection.
Source preprint: PRISM: A Plasmid-based Reporter for Intracellular Spectral Microscopy
- medrxiv2026-08-17score 73cardiologymetabolismcomputational
A 4.5-million-person HF GWAS puts myocardial energy, the mitochondrial proteome, and adipokines on the target list
Multi-ancestry GWAS of 345,687 heart-failure cases among 4,468,166 people, plus HFpEF and HFrEF splits, with plasma proteomics and multi-tissue transcriptomics, yields 383 loci (166 new) and 568 genes (375 new). Eleven new genes are already drug targets, including a case for expanding aldosterone-synthase inhibitors (CYP11B2) and type-II activin-receptor antagonists (ACVR2A) into HF. Nearly 100 genes sit in food intake, energy expenditure, fatty-acid/glucose/BCAA metabolism, and the mitochondrial proteome that sustains myocardial ATP. Metabolism and adipokines are framed as primordial HF targets.
Source preprint: Global genomics in over 4 million individuals prioritizes therapeutic targets for heart failure and its subtypes
- biorxiv2026-08-14score 72neurobiologytherapeuticsophthalmology
Cumulative IOP above 19 mmHg times RGC death; a mitochondria-targeted peptide still cuts the hazard
In DBA/2J glaucoma mice, retinal ganglion cell (RGC) loss is modeled as a latent time-to-event process driven by monthly intraocular pressure (IOP). Across Cox and Andersen–Gill models, cumulative IOP burden above 19 mmHg dominates the hazard. Peak and contemporaneous IOP add little once sustained exposure is in the model. HDAP2, a mitochondria-targeted neuroprotective peptide, significantly reduces progression hazard after adjustment for that longitudinal IOP exposure, which argues for a pressure-independent, organelle-directed effect.
Source preprint: Modeling Retinal Ganglion Cell Degeneration from Longitudinal Intraocular Pressure Trajectories
- biorxiv2026-08-13score 72neurobiologyagingmetabolism
CASIN restores aged α-synuclein brain networks along EGFR–PI3K–MAPK routes that feed mitochondria
In an inducible alpha-synuclein oligomer mouse, motor rescue by the CDC42 inhibitor CASIN is age-dependent, and single-nucleus RNA-seq now maps the transcriptional undo. CASIN robustly reverts Parkinson-related programs at 24 months; aging programs are loudest at 16 months. Networks converge on MAPK and PI3K/AKT, and the authors nominate an EGFR–PI3K–MAPK axis as the route by which CDC42 blockade may restore mitochondrial and synaptic function in aging and Parkinson disease.
Source preprint: Targeting CDC42 with CASIN Reprograms Cell Type Specific Transcriptomes and MAPK Driven Transcription Factor Networks in the Aging Brain
- biorxiv2026-08-19score 70mtDNAevolutiontranslation
Anomiida bivalves rewrite the mitochondrial code: TAA as tyrosine, plus frameshifting
Phylogenomics elevate the APPD bivalve clade (Anomiidae, Placunidae, Plicatulidae, and inferred Dimyidae) to Anomiida ord. nov., sister to Limida and Pectinoidea at about 428 million years. Their mitochondrial genomes show extreme translational plasticity: Pododesmus uses the invertebrate mitochondrial code; Heteranomia uses +1 frameshifting to skip in-frame TAG; Anomia, Enigmonia, Placuna, and Plicatulidae reassign TAA to tyrosine, confirmed by proteomics. That is a new bivalve translation table, sitting next to massive chromosomal fusions (6–13 chromosomes versus 20 ancestral molluscan linkage groups).
Source preprint: Life finds a way: Integrative phylogenomics resolves an overlooked bivalve order with chromosome fusion and mitochondrial translational-code evolution
- biorxiv2026-08-11score 70mtDNAcomputationalpopulation genetics
Medieval Sigtuna ivory is half eastern Atlantic walrus; attached rostra were a western trade
Earlier ancient-DNA work made medieval European walrus look almost entirely Greenlandic because it sampled decorated rostra (skulls with paired tusks). Workshop offcuts from Sigtuna, plus a genome-wide split between western and eastern Atlantic walrus populations (144,986 diagnostic nuclear SNPs, usable on low-coverage data), change that. All medieval rostra still assign west. About half the Sigtuna ivory assigns east, including Iceland and the Barents Sea, and the eastern objects come earlier. Mitochondrial DNA alone could not resolve this. The ivory trade was sequential and broader than the rostrum trade.
Source preprint: Of bone and ivory: Eastern Atlantic sources of the medieval European walrus ivory trade discovered by ancient mitochondrial and nuclear DNA
- biorxiv2026-08-19score 68mtDNAagingevolution
Long-lived termites write a stronger mitochondrial A>G signature all the way into the proteome
An age-associated mitochondrial A>G mutational signature, first described in mammals, is stronger in long-lived termites than in short-lived non-termite cockroaches. The extra A>G pressure is followed by coordinated shifts in synonymous nucleotide composition, codon usage, and amino acid composition. Life history can therefore travel from mutagen exposure through mtDNA spectra into the proteome. Mitochondrial genomes are archives of how a species lives, not only of who it is related to.
Source preprint: From life history to proteome via mutagenesis: an ecological footprint in genome evolution
- biorxiv2026-08-17score 64computationalcancerproteomics
ProtInt warps cell-line proteomes toward tumors and turns down mitochondrial gene-expression proteins
ProtInt is a deep-learning integrator that aligns label-free proteomes of 771 cancer cell lines and 550 treatment-naïve tumors despite missing values. It beats batch correction and transcriptomic-integration methods at making cell-line and tumor proteomes comparable. After integration, cell-line proteomes that have been warped toward tumors show recurrent gains in immune, cell–cell communication, and ECM proteins, and losses in transcription, RNA processing, and mitochondrial gene-expression proteins. The mitochondrial sentence is a systematic adaptation signature, not a functional assay.
Source preprint: Integration of proteomic data from cell lines and tumors
- biorxiv2026-08-12score 62computationalOXPHOSimmunology
PerturbLDM predicts unseen drug–dose–line transcriptomes and keeps an interferon FAO-OXPHOS program
PerturbLDM is a Tahoe-100M-pretrained latent-diffusion model that generates single-cell transcriptional responses to perturbations. On 13,942 held-out drug/dose/line combinations it beats leading methods and beats an additive marginal baseline in 95.2% of conditions. It ranks PANACEA compounds by pathway neighbors, builds a fetal-colon state more accurately than Squidiff, and in PBMCs captures six of seven interferon/antiviral programs plus an interferon-associated FAO-OXPHOS program better than scGen. The mitochondrial hook is that FAO-OXPHOS module, not a new metabolic mechanism.
Source preprint: PerturbLDM: conditional latent diffusion for modelling single-cell perturbation responses
- biorxiv2026-08-13score 60mtDNAmethodscomputational
pastForward finishes ancient libraries and screens them for eukaryotic mitochondria at scale
pastForward is a Snakemake pipeline from raw ancient/historical reads to damage-rescaled BAMs, with reports on endogenous content, complexity, and coverage. It maps to multiple references (host plus endosymbiont, COI). Two new tools: ECMSD screens libraries against a mitochondrial reference database for eukaryotic DNA; REVEAL quantifies copy-number of TEs and duplications. Case studies: AMY2B copy number rises across dog domestication including Neolithic samples; the TE opus invades D. melanogaster after the 1800s and is present from 1933. Mitochondria here are a taxonomic detector, not a physiology target.
Source preprint: pastForward: a Snakemake pipeline for ancient and historical DNA with eukaryote-wide taxonomic screening and tracking of copy-number variation