The cytochrome bc complexes found in mitochondria, chloroplasts and many bacteria catalyze a critical reaction in their respective electron transport chains. The quinol oxidase (Qo) site in this complex oxidizes a hydroquinone (quinol), reducing two one-electron carriers, a low-potential cytochrome b heme and a ‘Rieske’ iron-sulfur cluster. The overall electron transfer reactions are coupled to transmembrane translocation of protons via a ‘Q-cycle’ mechanism, which generates proton motive force for ATP synthesis. Since semiquinone intermediates of quinol oxidation are generally highly reactive, one of the key questions in this field is: how does the Qo site oxidize quinol without the production of deleterious side reactions including superoxide production? We attempt to test three possible general models to account for this behavior: 1) The Qo site semiquinone (or quinol:imidazolate complex) is unstable and thus occurs at a very low steady-state concentration, limiting O2 reduction; 2) the Qo site semiquinone is highly stabilized making it unreactive towards oxygen; and 3) the Qo site catalyzes a quantum mechanically-coupled two-electron/two proton transfer without a semiquinone intermediate. Enthalpies of activation were found to be almost identical between the uninhibited Q-cycle and superoxide production in the presence of Antimycin A in wild type. This behavior was also preserved in a series of mutants with altered driving forces for quinol oxidation. Overall, the data supports models where the rate-limiting step for both Q-cycle and superoxide production are essentially identical, consistent with model 1 but requiring modifications to models 2 and 3.
Revised: January 10, 2007 |
Published: December 15, 2006
Citation
Forquer I.P., R. Covian, M.K. Bowman, B. Trumpower, and D.M. Kramer. 2006.Similar Transition States Mediate the Q-cycle and Superoxide Production by the Cytochrome bc1 Complex.Journal of Biological Chemistry 281, no. 50:38459-38465. PNWD-SA-7426. doi:10.1074/jbc.M605119200