Effect of thiol modification on brain mitochondrial complex I activity

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