HIGH PROTONIC POTENTIAL ACTUATES A MECHANISM OF PRODUCTION OF REACTIVE OXYGEN SPECIES IN MITOCHONDRIA

Formation of H2O2 has been studied in rat heart mitochondria, pretreat ed,vith H2O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosp hate, malonate, rotenone and myxothiazol, and is stimulated by antimyc in A. The effect of ADP is abolished by carboxyatractylate and oligomy cin. Addition of uncoupler after rotenone induces further inhibition o f H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+P-i is shown to be proportional to the Delta Psi decrease by these compounds. A threshold Delta Psi value is found, above which a v ery strong increase in H2O2 production takes place. This threshold sli ghtly exceeds the state 3 Delta Psi level, The data obtained are in li ne with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169- 202] that a high proton motive force in state 4 is potentially dangero us for the cell due to an increase in the probability of superoxide fo rmation. (C) 1997 Federation of European Biochemical Societies.