Absence of a calmitine-specific protease inhibitor in skeletal muscle mitochondria of patients with Duchenne's muscular dystrophy.

We studied the effect of mitochondrial extracts from skeletal muscle of patients with Duchenne's muscular dystrophy (DMD) on calmitine from the skeletal muscle of normal mice and control subjects. Our results clearly show the existence of an abnormal proteolytic activity of mitochondria from patients with DMD on calmitine from the normal mouse. This proteolytic activity was not found on calmitine from the control subject. Overall, our observations suggest that calmitine concentration in the muscle of the control subject remains elevated because of the presence of a calmitine-specific protease and an inhibitor of this protease which regulates and/or suppresses the activity of the enzyme according to the requirements of the muscle cell. Conversely, the calmitine deficiency observed in the muscle of patients with DMD would be due to the absence of this inhibitor. This would account for the continual activity of the enzyme in degrading calmitine as soon as it is synthesized. The identification of this inhibitor is currently being investigated in our laboratory.