PNNL

Abstract

The mitochondrial cytochrome bc1 complex catalyzes the transfer of electrons from ubiquinol to cyt c, while generating a proton motive force for ATP synthesis, via the ‘Qcycle’ mechanism. Under certain conditions, electron flow through the Q-cycle is blocked at the level of a reactive intermediate in the quinol oxidase site of the enzyme, resulting in ‘bypass reactions’, some of which lead to superoxide production. Using analogs of the respiratory substrates, ubiquinol-3 and rhodoquinol-3, we show that the relative rates of Q-cycle bypass reactions in the Saccharomyces cerevisiae cyt bc1 complex are highly dependent, by a factor of up to one hundred-fold, on the properties of the substrate quinol. Our results suggest that the rate of Q-cycle bypass reactions is dependent on the steady state concentration of reactive intermediates produced at the quinol oxidase site of the enzyme. We conclude that normal operation of the Q-cycle requires a fairly narrow window of redox potentials, with respect to the quinol substrate, to allow normal turnover of the complex while preventing potentially damaging bypass reactions.