Reversible depolarization of in situ mitochondria by oxidative stress parallels a decrease in NAD(P)H level in nerve terminals

We have reported recently (Chinopoulos et al., 1999 J. Neurochem. 73, 220-2 28) that mitochondrial membrane potential (Delta Psi m) in isolated nerve t erminals is markedly reduced by H2O2 in the absence of F0F1-ATPase working as a proton pump. Here we demonstrate that Delta Psi m reduced by H2O2 (0.5 mM) in the presence of oligomycin (10 mu M), an inhibitor of the F0F1-ATPa se, was able to recover by the addition of catalase (2000 U). Similarly, a decrease in the NAD(P)H level due to H2O2 can be reversed by catalase. In a ddition, H2O2 decreased the ATP level and the [ATP]:[ADP] ratio measured in the presence of oligomycin reflecting an inhibition of glycolysis by H2O2. but this effect was not reversible. The effect of H2O2 on Delta Psi m in t he presence of the complex I inhibitor, rotenone, was also unaltered by add ition of catalase. These results provide circumstantial evidence for a rela tionship between the decreased NAD(P)H level and the inability of mitochond ria to maintain Delta Psi m during oxidative stress. (C) 2000 Elsevier Scie nce Ltd. All rights reserved.