High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria

FEBS Letters - Tập 416 Số 1 - Trang 15-18 - 1997
Sergey Korshunov1, Vladimir P. Skulachev1, Anatoly A. Starkov1
1Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia

Tóm tắt

Formation of H2O2 has been studied in rat heart mitochondria, pretreated with 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 phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the ΔΨ decrease by these compounds. A threshold ΔΨ value is found, above which a very strong increase in H2O2 production takes place. This threshold slightly exceeds the state 3 ΔΨ level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169–202] that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation.

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FEBS Letters

Tập 416 Số 1

15-18

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