Architecture of mammalian respiratory complex I.

TitleArchitecture of mammalian respiratory complex I.
Publication TypeJournal Article
Year of Publication2014
AuthorsVinothkumar, KR, Zhu, J, Hirst, J
JournalNature
Volume515
Issue7525
Pagination80-4
Date Published2014 Nov 6
ISSN1476-4687
KeywordsAnimals, Cattle, Cryoelectron Microscopy, Electron Transport Complex I, Mitochondria, Heart, Models, Molecular, Protein Structure, Tertiary, Protein Subunits
Abstract

Complex I (NADH:ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the energy-transducing inner membrane, providing electrons for respiration and driving ATP synthesis. Mammalian complex I contains 44 different nuclear- and mitochondrial-encoded subunits, with a combined mass of 1 MDa. The 14 conserved 'core' subunits have been structurally defined in the minimal, bacterial complex, but the structures and arrangement of the 30 'supernumerary' subunits are unknown. Here we describe a 5 Å resolution structure of complex I from Bos taurus heart mitochondria, a close relative of the human enzyme, determined by single-particle electron cryo-microscopy. We present the structures of the mammalian core subunits that contain eight iron-sulphur clusters and 60 transmembrane helices, identify 18 supernumerary transmembrane helices, and assign and model 14 supernumerary subunits. Thus, we considerably advance knowledge of the structure of mammalian complex I and the architecture of its supernumerary ensemble around the core domains. Our structure provides insights into the roles of the supernumerary subunits in regulation, assembly and homeostasis, and a basis for understanding the effects of mutations that cause a diverse range of human diseases.

DOI10.1038/nature13686
Alternate JournalNature
Citation Key10.1038/nature13686
PubMed ID25209663
PubMed Central IDPMC4224586
Grant ListMC_U105184322 / / Medical Research Council / United Kingdom
MC_U105663141 / / Medical Research Council / United Kingdom
U105184322 / / Medical Research Council / United Kingdom
U105663141 / / Medical Research Council / United Kingdom