Role of zinc as an activator of mitochondrial function in rat liver

The effects of zinc on the enzymes of hepatic mitochondria were investigated in rats that had been given zinc sulfate (10 mg Zn2+/100 g body wt) p.o. Administration of zinc caused a marked elevation of succinate dehydrogenase, glutamate dehydrogenase, cytochrome c oxidase and ATPase activities, whereas it did not cause significant changes in pyruvate carboxylase, malate dehydrogenase and isocitrate dehydrogenase activities. The effect of zinc as a function of time was greatest on succinate dehydrogenase. Zinc also produced a marked elevation of ATP concentration in the hepatic cytosol and a corresponding increase in ATPase activity in the hepatic mitochondria. Zinc content of the inner membrane of mitochondria was raised significantly by administration of zinc. The removal of zinc by washing in 10 mM EDTA caused a significant decrease of the increased succinate dehydrogenase activity caused by administration of zinc, while it did not lower ATPase activity. The addition of zinc in amounts of 10-10(3) ng Zn2+ per mg protein produced a significant increase in succinate dehydrogenase activity in the inner membrane of mitochondria, whereas ATPase activity was elevated significantly at 10(3)-10(4) ng Zn2+ per mg protein, indicating that zinc activated succinate dehydrogenase more sensitively than ATPase. The present investigation suggests that zinc taken up by hepatic mitochondria stimulates the electron transport system and oxidative phosphorylation and, as a result, increases the ATP concentration in the hepatic cytosol.