Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.

TitleCryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states.
Publication TypeJournal Article
Year of Publication2018
AuthorsAgip, A-NA, Blaza, JN, Bridges, HR, Viscomi, C, Rawson, S, Muench, SP, Hirst, J
JournalNat Struct Mol Biol
Date Published2018 07
KeywordsAnimals, Binding Sites, Cryoelectron Microscopy, Electron Transport Complex I, Enzyme Activation, Mice, Mitochondria, Heart, Models, Molecular, NADH Dehydrogenase, Nucleotides, Phospholipids, Protein Structural Elements, Protein Structure, Quaternary, Protein Subunits, Ubiquinone

Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia-reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the 'active' state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the 'deactive' state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I.

Alternate JournalNat. Struct. Mol. Biol.
Citation Key10.1038/s41594-018-0073-1
PubMed ID29915388
PubMed Central IDPMC6054875
Grant List / / Wellcome Trust / United Kingdom
MC_U105663141 / / Medical Research Council / United Kingdom