Hamster cardiomyopathy. A defect in oxidative phosphorylation in the cardiac interfibrillar mitochondria.

To determine whether or not an oxidative defect exists in hearts of cardiomyopathic (BIO 14.6) hamsters, cardiac tissue and subcellular organelles were studied.Using homogenates of hearts, the sarcolemmal marker, 5'-nucleotidase, was decreased, whereas the lysosomal enzymes, acid phosphatase and N-acetylglucosaminidase, were increased in the cardiomyopathic hearts compared to controls.The mitochondrial enzymes, enoyl-CoA hydratase, P-hydroxyacyl-CoA dehydrogenase, and citrate synthase, were depressed in the cardiomyopathic hearts.The content of coenzyme A was unaltered, but the content of carnitine was depressed in the cardiomyopathic hearts.Just as in normal hamster hearts, two populations of mitochondria were present in the hearts of the cardiomyopathic hamsters.Oxidative phosphorylation b y subsarcolemmal mitochondria was similar in the controls and in the cardiomyopathic hearts.State 3, ADPstimulated respiration was significantly decreased in interfibrillar mitochondria from the cardiomyopathic hearts compared to the same mitochondria from controls.This decrease was seen with both NAD-and FADlinked substrates.Analysis of mitochondrial enzymes did not provide an explanation f o r the depressed oxidation rates.The content of cytochromes cl, c, b, and aa3 was not altered in the cardiomyopathic mitochondria compared to controls.NADH oxidase also was not affected by the cardiomyopathic process.The properties of the mitochondrial inner membrane, possibly involving transport, m a y be responsible f o r the changes in state 3 respiration in interfibrillar mitochondria in the cardiomyopathic hamster heart.W e conclude that a mitochondrial oxidative defect is present in cardiac muscle cells in cardiomyopathic hamsters, but that it is confined wholly to the interfibrillar mitochondria.O u r observations thus reconcile the disparate findings of other investigators.