A ternary mechanism for NADH oxidation by positively charged electron acceptors, catalyzed at the flavin site in respiratory complex I.

TitleA ternary mechanism for NADH oxidation by positively charged electron acceptors, catalyzed at the flavin site in respiratory complex I.
Publication TypeJournal Article
Year of Publication2011
AuthorsBirrell, JA, King, MS, Hirst, J
JournalFEBS Lett
Volume585
Issue14
Pagination2318-22
Date Published2011 Jul 21
ISSN1873-3468
KeywordsAdenosine Diphosphate, Adenosine Diphosphate Ribose, Adenosine Triphosphate, Animals, Cattle, Electron Transport Complex I, Electrons, Flavins, Herbicides, Mitochondria, Heart, NAD, Oxidation-Reduction, Paraquat, Ruthenium Compounds
Abstract

The flavin mononucleotide in complex I (NADH:ubiquinone oxidoreductase) catalyzes NADH oxidation, O(2) reduction to superoxide, and the reduction of several 'artificial' electron acceptors. Here, we show that the positively-charged electron acceptors paraquat and hexaammineruthenium(III) react with the nucleotide-bound reduced flavin in complex I, by an unusual ternary mechanism. NADH, ATP, ADP and ADP-ribose stimulate the reactions, indicating that the positively-charged acceptors interact with their negatively-charged phosphates. Our mechanism for paraquat reduction defines a new mechanism for superoxide production by complex I (by redox cycling); in contrast to direct O(2) reduction the rate is stimulated, not inhibited, by high NADH concentrations.

DOI10.1016/j.febslet.2011.05.065
Alternate JournalFEBS Lett.
Citation Key10.1016/j.febslet.2011.05.065
PubMed ID21664911
Grant ListMC_U105663141 / / Medical Research Council / United Kingdom