The ubiquinol/bc(1) redox couple regulates mitochondrial oxygen radical formation

The generation of oxygen radicals in biological systems and their sites of intracellular release were subject of numerous studies in the last decades. Based on these studies mitochondria were considered as the major source of intracellular oxygen radicals. Although this finding is more or less accep ted the mechanism of univalent oxygen reduction in mitochondria is still ob scure. One of the most critical electron transfer steps of the respiratory chain is the electron bifurcation at the be, complex, From recent; studies with genetically mutated mitochondria it became clear that electron bifurca tion from ubiquinol to the be, complex requires an underanged mobility of t he head domain of the Rieske iron sulfur protein. On the other hand it is l ong known that inhibition of electron bifurcation by antimycin A causes the leakage of single electrons to dioxygen, which results in the release of O -2(.-) radicals. These findings made us to prove whether the impediment of the interaction of ubiquinol with the be, complex is the regulator of singl e electron diversion to oxygen. Impediment of electron bifurcation was obse rved following alterations of the physical state of membrane phospholipids in which the be, complex is inserted. Irrespectively, whether the fluidity of membrane lipids was elevated or decreased electron how rates to the Ries ke iron sulfur protein and to low potential cytochrome b were drastically r educed. Concomitantly O-2(.-) radicals were released from these mitochondri a, suggesting an effect on the mobility of the head domain of the Rieske ir on sulfur protein. These results including the well known effect of antimyc in A revealed the involvement of the ubiquinol be, redox couple in mitochon drial O-2(.-) formation. The regulator which controls leakage of electrons to oxygen appears to be the electron branching activity of the be, complex. (C) 2001 Academic Press.