{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Olahova M"],"funding":["Mito Foundation","Deutsche Forschungsgemeinschaft (DFG)","LifeArc","Barbour Foundation UK","HHS | National Institutes of Health (NIH)","NIHR | NIHR Newcastle Biomedical Research Centre (Newcastle Biomedical Research Centre)","Academy of Medical Sciences","German Federal Ministry of Education and Research","HHS | National Institutes of Health","Lily Foundation","Pathological Society of Great Britain and Ireland","NIHR | NIHR Newcastle Biomedical Research Centre","Deutsche Forschungsgemeinschaft","Biochemical Society","Lily Foundation (Lily)","Fight for Sight UK","NINDS NIH HHS","UK NHS Highly Specialised Service for Rare Mitochondrial Disorders","Wellcome Trust","BJC Investigator Program","Mito Foundation (Mito)"],"pagination":["5482-5508"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12489013"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(19)"],"pubmed_abstract":["A biochemical deficiency of mitochondrial complex I (CI) underlies approximately 30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants in RTN4IP1, a gene that encodes a mitochondrial NAD(P)H oxidoreductase. Here, we demonstrate that RTN4IP1 deficiency causes a CI assembly defect in both patient fibroblasts and knockout cells, and report that RTN4IP1 is a bona fide CI assembly factor. Complexome profiling revealed accumulation of unincorporated ND5-module and impaired N-module production. RTN4IP1 patient fibroblasts also exhibited defective coenzyme Q biosynthesis, substantiating a second function of RTN4IP1. Thus, our"],"journal":["The EMBO journal"],"pubmed_title":["RTN4IP1 is required for the final stages of mitochondrial complex I assembly and CoQ biosynthesis."],"pmcid":["PMC12489013"],"funding_grant_id":["SFB1531","N/A","R01 NS112381","WI 3728/1-1","R01NS112381","R35GM131795","mitoNET 01GM1906D","WI-3728/3-1","203105/Z/16/Z","R01 NS131322","R01NS131322"],"pubmed_authors":["Heidler J","Collier JJ","Wittig I","Guerra RM","Olahova M","Thompson K","Lightowlers RN","White CR","Galkin A","Pagliarini DJ","Taylor RW","Cabrera-Orefice A","Chrzanowska-Lightowlers ZMA","Castaneda-Tamez P"],"additional_accession":[]},"is_claimable":false,"name":"RTN4IP1 is required for the final stages of mitochondrial complex I assembly and CoQ biosynthesis.","description":"A biochemical deficiency of mitochondrial complex I (CI) underlies approximately 30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants in RTN4IP1, a gene that encodes a mitochondrial NAD(P)H oxidoreductase. Here, we demonstrate that RTN4IP1 deficiency causes a CI assembly defect in both patient fibroblasts and knockout cells, and report that RTN4IP1 is a bona fide CI assembly factor. Complexome profiling revealed accumulation of unincorporated ND5-module and impaired N-module production. RTN4IP1 patient fibroblasts also exhibited defective coenzyme Q biosynthesis, substantiating a second function of RTN4IP1. Thus, our","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T01:54:01.315Z","creation":"2026-05-04T03:14:07.805Z"},"accession":"S-EPMC12489013","cross_references":{"pubmed":["40859035"],"doi":["10.1038/s44318-025-00533-x"]}}