Mitochondrial protein phosphorylation and cardiomyopathy in genetically diabetic mice: the effect of estrone...

The alpha-subunit of pyruvate dehydrogenase and succinyl-CoA synthetase are phosphorylated after incubation of cardiac mitochondria from genetically diabetic mice with [gamma-32P]ATP. There is significantly increased incorporation of 32P into pyruvate dehydrogenase from diabetic mice when compared to controls. The enhanced rate of pyruvate dehydrogenase phosphorylation correlates well with the previously reported defective oxidative metabolism and decreased activity of this enzyme from diabetic mice. The relationship between abnormal mitochondrial function and development of cardiomyopathy in the diabetic mice has been studied further by in vivo estrone treatment. The results indicate that ultrastructural alterations of myocardium are closely associated with the defective pyruvate oxidation (via phosphorylation of pyruvate dehydrogenase) and both processes can be prevented by 7-12 weeks estrone treatment.