Structure of the Deactive State of Mammalian Respiratory Complex I.

TitleStructure of the Deactive State of Mammalian Respiratory Complex I.
Publication TypeJournal Article
Year of Publication2018
AuthorsBlaza, JN, Vinothkumar, KR, Hirst, J
Date Published2018 Feb 06

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles.

Alternate JournalStructure
Citation Key10.1016/j.str.2017.12.014
PubMed ID29395787
PubMed Central IDPMC5807054
Grant List / / Wellcome Trust / United Kingdom