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Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits.","is_dataset_classified":null,"base_score":5.0369526024136295,"endowment":5.0369526024136295,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33465056","pmcid":"PMC7954600","openalex_id":"https://openalex.org/W3123153443","authors":[],"funders":[{"funder_name":"German Federal Ministry of Education and Research (BMBF, Bonn, Germany) grant to the German Network for Mitochondrial Disorders","grant_id":"01GM1906D,01GM1906A","title":null},{"funder_name":"German BMBF and Horizon2020 through the E-Rare project GENOMIT","grant_id":"01GM1603","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"SFB 815/Z1","title":null},{"funder_name":"Italian Ministry of Health","grant_id":"GR-2016-02361449","title":null},{"funder_name":"Italian Ministry of Health","grant_id":"Ricerca Corrente","title":null},{"funder_name":"Cardio Pulmonary Institute (CPI) of the DFG","grant_id":"EXC2026","title":null},{"funder_name":"Austrian Science Fund FWF","grant_id":"I 4695","title":"GENOMIT - Global registry, genomics, toward clinical trials"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"61867463/SFB 815","title":"Redox-Regulation: Generatorsysteme und funktionelle Konsequenzen"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Institute for Health Research (NIHR)","grant_id":"","title":null}],"total_grants":10,"fwci":9.1058,"citation_percentile":0.98887741,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":20},{"year":2022,"count":41},{"year":2023,"count":30},{"year":2024,"count":32},{"year":2025,"count":19},{"year":2026,"count":9}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jci.org/articles/view/138267/files/pdf","host_type":"journal"},{"url":"http://www.jci.org/articles/view/138267/files/pdf","host_type":"publisher"},{"url":"https://www.jci.org/articles/view/138267/files/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1172/jci138267","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33465056","host_type":"repository"},{"url":"http://hdl.handle.net/2434/863462","host_type":"repository"},{"url":"https://hdl.handle.net/11585/864665","host_type":"repository"},{"url":"https://epub.ub.uni-muenchen.de/102329/","host_type":"repository"},{"url":"https://mediatum.ub.tum.de/1593914","host_type":"repository"},{"url":"https://mediatum.ub.tum.de/1655317","host_type":"repository"},{"url":"https://pub.dzne.de/search?p=id:%22DZNE-2021-01184%22","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7954600","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7954600","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7954600?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1172/JCI138267","host_type":""},{"url":"https://dx.doi.org/10.1172/jci138267","host_type":""},{"url":"https://pub.dzne.de/record/157727","host_type":""},{"url":"https://doi.org/10.1172/JCI138267","host_type":""},{"url":"https://hdl.handle.net/2434/863462","host_type":""},{"url":"https://push-zb.helmholtz-munich.de/frontdoor.php?source_opus=61088","host_type":""},{"url":"https://hdl.handle.net/2318/2029804","host_type":""}],"fields_of_study":["Mitochondrial Function and Pathology","ATP Synthase and ATPases Research","Cell death mechanisms and regulation","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Adolescent","Adult","Cell Line","Child, Preschool","Female","Genes, Recessive","Homozygote","Humans","Male","Middle Aged","Mutation","Pedigree","Phenotype","Reactive Oxygen Species","Penetrance","Protein Subunits","Optic Atrophy, Hereditary, Leber","Electron Transport Complex I","HSP40 Heat-Shock Proteins","Gene Knockout Techniques","Young Adult"],"keywords":["Medicine","Leber's hereditary optic neuropathy","Optic neuropathy","Genetics","Biology","Ophthalmology","Optic nerve","Neuroscience","Genetic diseases","Adult","Male","Adolescent","Genes, Recessive","Penetrance","Optic Atrophy, Hereditary, Leber","Genetic diseases; 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