Reversible effect of calcium-binding protein on the Ca2+-induced activation of succinate dehydrogenase in rat liver mitochondoria.

Abstract

The effect of calcium-binding protein (CaBP) isolated from rat liver cytosol on the Ca2+-induced increase in succinate dehydrogenase activity of rat liver mitochondria was investigated. The liver mitochondrial succinate dehydrogenase activity was significantly increased by addition of Ca2+ in the range of 1.0-50 .mu.M. Of various other metals (25 .mu.M) tested, addition of Hg2+, Zn2+ and Cd2+ caused a significant decrease in succinate dehydrogenase activity of the hepatic mitochondria, while Mg2+, Mn2+ and Sr2+ had no effect; the increase in the enzyme activity was specific for Ca2+. This Ca2+-induced increase in the mitochondrial succinate dehydrogenase activity was completely blocked by the presence of ruthenium red (10 and 50 .mu.M), an inhibitor of mitochondrial Ca2+ uptake, indicating that Ca2+ was transported into the mitochondria and activated the enzyme there. In the presence of more than 7.0 .mu.M CaBP, the Ca2+ (10 .mu.M)-induced increase in succinate dehydrogenase activity was completely reversed, but 1.4 .mu.M CaBP had no effect on this increase. CaBP itself (15 .mu.M) did not have an inhibitory effect on the basal activity of succinate dehydrogenase. The present results suggest that CaBP regulates the increase in succinate dehydrogenase activity by blocking Ca2+ transport into the hepatic mitochondria of rats.