The respiratory substrate rhodoquinol induces Q-cycle bypass reactions in the yeast cytochrome bc(1) complex: mechanistic and physiological implications.
The mitochondrial cytochrome bc(1) complex catalyzes the transfer of electrons from ubiquinol to cyt c while generating a proton motive force for ATP synthesis via the "Q-cycle" 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 bc(1) complex are highly dependent by a factor of up to 100-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.
Cape
Jonathan L
JL
Institute of Biological Chemistry, Washingston State University, Pullman, Washington 99164-6340, USA.
Strahan
Jeff R
JR
Lenaeus
Michael J
MJ
Yuknis
Brook A
BA
Le
Trieu T
TT
Shepherd
Jennifer N
JN
Bowman
Michael K
MK
Kramer
David M
DM
D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D004563:Electrochemistry; D014450:Electron Transport Complex III / Q000737:chemistry* / Q000378:metabolism; D004583:Electrons; D007700:Kinetics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry; D010101:Oxygen Consumption; D011485:Protein Binding; D011522:Protons; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013379:Substrate Specificity; D013481:Superoxides / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D011522:Protons; C506087:rhodoquinone-3; D013481:Superoxides; D014451:Ubiquinone; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D014450:Electron Transport Complex III