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.
Balijepalli
S
S
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Annepu
J
J
Boyd
M R
MR
Ravindranath
V
V
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D042967:Electron Transport Complex I; D005033:Ethylmaleimide / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D019807:Iodoacetic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013438:Sulfhydryl Compounds / Q000502:physiology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D005978:Glutathione; D005033:Ethylmaleimide; D019807:Iodoacetic Acid