Respiratory complex II: ROS production and the kinetics of ubiquinone reduction.
Bovine heart mitochondrial respiratory complex II generates ROS, mostly as superoxide, at the rate of about 20% of that detected during simultaneous operation of complex I and II when oxidation of ubiquinol is prevented by myxothiazol. ROS generating activity at different fumarate/succinate concentrations ratio implies that an enzyme component with a midpoint potential 40mV more positive than that of fumarate/succinate couple is the donor for one-electron reduction of oxygen. This suggests that the iron-sulfur cluster(s) is(are) involved in superoxide formation. Complex II-mediated ROS production exhibits a maximum at low (about 50μM) succinate concentration and gradually declines to zero activity upon further increase of the substrate. This phenomenology is explained and kinetically modeled to suggest a ping-pong mechanism of ROS generating activity where only dicarboxylate free reduced enzyme is oxidized by oxygen. The succinate:quinone reductase activity catalyzed by purified succinate:ubiquinone reductase also exhibits a ping-pong mechanism where only dicarboxylate free enzyme is oxidized by added quinone. Together these data suggest long distance interaction between the succinate (fumarate) binding and ubiquinone (ubiquinol) reactive sites.
Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, Russian Federation.
Vera G
VG
Grivennikova
Belozersky Institute of Physical-Chemical Biology, Moscow State University, Moscow 119991, Russian Federation.
Vladimir S
VS
Kozlovsky
Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, Russian Federation. Electronic address: adv@biochem.bio.msu.su.
Andrei D
AD
Vinogradov
D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism*; D005650:Fumarates / Q000378:metabolism; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
D005650:Fumarates; D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species; C478189:respiratory complex II; D013481:Superoxides; D014451:Ubiquinone; D019802:Succinic Acid; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I
Hydrogen peroxide; Mitochondria; Respiratory complex II; Succinate dehydrogenase; Superoxide anion; Ubiquinone reduction