{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liang C"],"funding":["Ministerio de Ciencia, Innovación y Universidades","NIDDK NIH HHS","Howard Hughes Medical Institute","Duke University School of Medicine","Karolinska Institutet","Ministry of Education - Singapore","National Health and Medical Research Council","National Medical Research Council","National Institutes of Health","National Research Foundation","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["441-459.e11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11892702"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["37(2)"],"pubmed_abstract":["Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I<sub>2</sub>+III<sub>2</sub>, resolved at 3.7 Å by cryoelectron microscopy (cryo-EM). SC-XL formation increases mitochondrial cristae density, reduces CIII reactive oxygen species (ROS), and sustains normal respiration despite a 70% reduction in CIII activity, effectively rescuing CIII deficiency. Consequently, inhibiting SC-XL formation in CIII mutants using the U"],"journal":["Cell metabolism"],"pubmed_title":["Formation of I&lt;sub&gt;2&lt;/sub&gt;+III&lt;sub&gt;2&lt;/sub&gt; supercomplex rescues respiratory chain defects."],"pmcid":["PMC11892702"],"funding_grant_id":["R01 GM144613","MOH-001394","R35GM137929","GNT2009732","R01 DK127979","GNT1140906","MOH-000960","PID2023-147288NB-I00","HR24-00604","R01 DK107397","R35 GM137929"],"pubmed_authors":["Lim R","Wittig I","Muoio D","Beh S","Osaka H","Zhang S","Wu YJ","Ugalde C","Liang C","Meisterknecht J","Robinson DRL","Watanabe C","Kappei D","Koves TR","Watanabe M","Cabrera-Orefice A","Ren S","Funai K","Letts JA","Johnson JM","Illescas M","Ghelli AM","Ho L","Stroud DA","Padavannil A"],"additional_accession":[]},"is_claimable":false,"name":"Formation of I&lt;sub&gt;2&lt;/sub&gt;+III&lt;sub&gt;2&lt;/sub&gt; supercomplex rescues respiratory chain defects.","description":"Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I<sub>2</sub>+III<sub>2</sub>, resolved at 3.7 Å by cryoelectron microscopy (cryo-EM). SC-XL formation increases mitochondrial cristae density, reduces CIII reactive oxygen species (ROS), and sustains normal respiration despite a 70% reduction in CIII activity, effectively rescuing CIII deficiency. Consequently, inhibiting SC-XL formation in CIII mutants using the U","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-07-15T13:29:44.741Z","creation":"2026-07-05T03:08:17.198Z"},"accession":"S-EPMC11892702","cross_references":{"pubmed":["39788125"],"doi":["10.1016/j.cmet.2024.11.011"]}}