{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Meisel JD"],"funding":["NIA NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["659-675.e18"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10919891"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["187(3)"],"pubmed_abstract":["The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C. elegans and are specific to mutants that compromise the electron-conducting matrix arm. We show that hypoxia rescue does not involve the hypoxia-inducible factor pathway or attenuation of reactive oxygen species. To discover the mechanism, we use C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6/nuo-3 that phenocopy hypoxia rescue. We show t"],"journal":["Cell"],"pubmed_title":["Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism."],"pmcid":["PMC10919891"],"funding_grant_id":["R56 AG016636","F32 GM133047","K99 GM140217","R01 GM044619","R01 AG016636","R01 NS124679"],"pubmed_authors":["Wellner SM","Jourdain AA","Mootha VK","Miranda M","Ruvkun G","Wiesenthal PP","Meisel JD","Skinner OS"],"additional_accession":[]},"is_claimable":false,"name":"Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism.","description":"The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C. elegans and are specific to mutants that compromise the electron-conducting matrix arm. We show that hypoxia rescue does not involve the hypoxia-inducible factor pathway or attenuation of reactive oxygen species. To discover the mechanism, we use C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6/nuo-3 that phenocopy hypoxia rescue. We show t","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-01T05:46:22.04Z","creation":"2025-04-05T19:19:27.772Z"},"accession":"S-EPMC10919891","cross_references":{"pubmed":["38215760"],"doi":["10.1016/j.cell.2023.12.010"]}}