| 3214168 |
Moore GA, Weis M, Orrenius S, O'Brien PJ: Role of sulfhydryl groups in benzoquinone-induced Ca2+ release by rat liver mitochondria. Arch Biochem Biophys. 1988 Dec;267(2):539-50.
Incubation of rat liver mitochondria with benzoquinone derivatives in the presence of succinate plus rotenone has been shown to cause NAD (P) H oxidation followed by Ca2+ release. Further investigation revealed: (1) p-Benzoquinone-induced Ca2+ release was not initiated by a collapse of the mitochondrial membrane potential. However, Ca2+ release and subsequent Ca2+ cycling caused limited increased membrane permeability. (2) p-Benzoquinone-induced NAD (P) H oxidation and Ca2+ release were prevented by isocitrate, 3-hydroxybutyrate, and glutamate but not by pyruvate or 2-oxoglutarate. (3) Inhibition of pyruvate and 2-oxoglutarate dehydrogenases by p-benzoquinone was attributed to arylation of the SH groups of the cofactors, CoA and lipoic acid. Isocitrate dehydrogenase was also inhibited by p-benzoquinone, but the cofactors NAD (P) H and Mn2+ protected the enzyme. Glutamate dehydrogenase was not inhibited by p-benzoquinone. (4) Arylation of mitochondrial protein thiols by p-benzoquinone was associated with an inhibition of state 3 respiration, which was attributed to the inactivation of the phosphate translocase. In contrast, state 4 respiration, and the F1.F0-ATPase and ATP/ADP translocase activities were not inhibited. It was concluded that inhibition of mitochondrial NAD (P) H dehydrogenases by arylation of critical thiol groups will decrease the NAD (P)+-reducing capacity, and possibly lower the NAD (P) H/NAD (P)+ redox status in favor of Ca2+ release. |
0(0,0,0,0) |