title: Energy conversion, redox catalysis and generation of reactive oxygen species by respiratory complex I.
abstract: Complex I (NADH:ubiquinone oxidoreductase) is critical for respiration in mammalian mitochondria. It oxidizes NADH produced by the Krebs' tricarboxylic acid cycle and β-oxidation of fatty acids, reduces ubiquinone, and transports protons to contribute to the proton-motive force across the inner membrane. Complex I is also a significant contributor to cellular oxidative stress. In complex I, NADH oxidation by a flavin mononucleotide, followed by intramolecular electron transfer along a chain of iron-sulfur clusters, delivers electrons and energy to bound ubiquinone. Either at cluster N2 (the terminal cluster in the chain) or upon the binding/reduction/dissociation of ubiquinone/ubiquinol, energy from the redox process is captured to initiate long-range energy transfer through the complex and drive proton translocation. This review focuses on current knowledge of how the redox reaction and proton transfer are coupled, with particular emphasis on the formation and role of semiquinone intermediates in both energy transduction and reactive oxygen species production. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, United Kingdom. Electronic address: jh@mrc-mbu.cam.ac.uk.
authors.forename: Judy
authors.initials: J
authors.lastname: Hirst
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom. Electronic address: m.roessler@qmul.ac.uk.
authors.forename: Maxie M
authors.initials: MM
authors.lastname: Roessler
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000648:ultrastructure*; D004735:Energy Transfer; D004789:Enzyme Activation; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D009243:NAD / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D011485:Protein Binding; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000138:chemical synthesis*; D014451:Ubiquinone / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D017382:Reactive Oxygen Species; D009243:NAD; D014451:Ubiquinone; D042967:Electron Transport Complex I
keywords: Electron paramagnetic resonance; Iron–sulfur cluster; NADH:ubiquinone oxidoreductase; Proton-coupled electron transfer; Semiquinone; Superoxide