Effect of thiol modification on brain mitochondrial complex I activity

We have studied the effect of altered thiol status on brain mitochondrial complex I activity. Exposure of mouse brain slices to diethyl maleate resulted in significant loss in complex I activity with concomitant loss of thiol antioxidant, glutathione. However, incubation of mitochondria isolated from diethyl maleate treated slices with dithiothreitol completely regenerated activity of complex I. Incubation of mouse brain slices with iodoacetic acid, a thiol modifier, also resulted in inhibition of complex I activity, which was reversed by glutathione. The present study demonstrates sensitivity of complex I to thiol modifying agents. Reversal of this inhibition by thiol reductants indicates that secondary oxidation of thiol groups in complex I as a consequence of thiol modification is responsible for the loss in activity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.