Ca2+-induced activation of succinate dehydrogenase and the regulation of mitochondrial oxidative reactions.
1. In rat liver mitochondria in vitro, an activation of succinate dehydrogenase [succinate: (2,6-dichloroindophenol)oxido-reductase], an inner membrane enzyme, was induced by Ca2+ at extramitochondrial concentrations (about 1.3 micron) close to those estimated in the cytosol. 2. The activation required both substrate (succinate) and ATP, and occurred whether mitochondria were coupled (Ca2+ could be accumulated) or uncoupled (Ca2+ could not be accumulated) by classical uncouplers. 3. The activation by Ca2+ of the uncoupled mitochondria was accompanied by a modest but significant change in the mitochondrial morphology as judged from light scattering measurements and electron microscopy. 4. In the uncoupled mitochondria, oxaloacetate added externally diminished the activation by Ca2+. In addition, the amount of oxaloacetate produced endogenously from succinate via malate fell after Ca2+ and ATP addition. However, the extent of the fall in mitochondrial oxaloacetate did not correlate with the degree of activation of succinate dehydrogenase. 5. The activation by Ca2+ of the uncoupled mitochondria was accompanied by a reductive shift of pyridine nucleotide and coenzyme Q, and an oxidative shift of flavoproteins and cytochromes b, c, and a-a3. 6. In the situation where the Ca2+-induced activation of succinate dehydrogenase (and consequently succinate oxidation) took place in the uncoupled mitochondria, oxidations of 3-hydroxybutyrate and pyruvate were markedly suppressed. 7. From the above findings, it is concluded that Ca2+ action on the mitochondrial inner membrane activates mitochondrial succinate dehydrogenase, and this action produces an inhibition of electron transport between NAD and flavoprotein. In view of the location of these reactions in the inner membrane, a conformation change of the membrane is suggested as a common cause.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004789:Enzyme Activation; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000648:ultrastructure; D010071:Oxaloacetates / Q000378:metabolism; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism*
D008293:Malates; D010071:Oxaloacetates; D013385:Succinate Dehydrogenase; D002118:Calcium