A model of O•2- generation in the complex III of the electron transport chain

Oxidation of semiquinone by O-2 in the Q cycle is known to be one of the sources of superoxide anion (O .(-)(2)) in aerobic cells. In this paper, such a phenomenon was analyzed using the chemical kinetics model of electron transfer from succinate to cytochrome c, including coenzyme Q, the complex III non-heme iron protein FeSIII and cytochromes b(1), b(h) and c(1). Electron transfers from QH(2) to FeSIII and cytochrome b(1) were assumed to occur according to direct transfer mechanism (dynamic channelling) involving the formation of FeSIIIred -Q.(-) and Q.(-)-cytochrome b(1) complexes. For oxidation/reduction reactions involving cytochromes b(h) and b(1), the dependence of the equilibrium and elementary rate constants on the membrane potential (Delta psi) was taken into consideration. The rate of O .(-)(2) generation was found to increase dramatically with increase in Delta psi above the values found in State 3. On the other hand, the rate of cytochrome c reduction decreased sharply at the same values of the membrane potential. This explains experimental data that the O .(2)- generation at State 4 appears to be very much faster than at State 3. A mild uncoupling in State 4 can markedly decrease the superoxide generation due to a decrease in Delta psi below the above mentioned critical level. Delta pH appears to be equally effective as Delta psi in stimulation of superoxide production which depends, in fact, upon the Delta<(mu)over bar>(H)+ level.