IMPAIRED MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION IN SKELETAL-MUSCLE OF THE DYSTROPHIN-DEFICIENT MDX MOUSE

The mdx mouse, an animal model of the Duchenne muscular dystrophy, was used for the investigation of changes in mitochondrial function assoc iated with dystrophin deficiency. Enzymatic analysis of skeletal muscl e showed an approximately 50% decrease in the activity of all respirat ory chain-linked enzymes in musculus quadriceps of adult mdx mice as c ompared with controls, while in cardiac muscle no difference was obser ved. The activities of cytosolic and mitochondrial matrix enzymes were not significantly different from the control values in both cardiac a nd skeletal muscles. In saponin-permeabilized skeletal muscle fibers o f mdx mice the maximal rates of mitochondrial respiration were about t wo times lower than those of controls. These changes were also demonst rated on the level of isolated mitochondria. Mdx muscle mitochondria h ad only 60% of maximal respiration activities of control mice skeletal muscle mitochondria and contained only about 60% of hemoproteins of m itochondrial inner membrane. Similar findings were observed in a skele tal muscle biopsy of a Duchenne muscular dystrophy patient. These data strongly suggest that a specific decrease in the amount of all mitoch ondrial inner membrane enzymes, most probably as result of Ca2+ overlo ad of muscle fibers, is the reason for the bioenergetic deficits in dy strophin-deficient skeletal muscle.