ABSENCE OF A CALMITINE-SPECIFIC PROTEASE INHIBITOR IN SKELETAL-MUSCLEMITOCHONDRIA OF PATIENTS WITH DUCHENNES MUSCULAR-DYSTROPHY

We studied the effect of mitochondrial extracts from skeletal muscle o f patients with Duchenne's muscular dystrophy (DMD) on calmitine from the skeletal muscle of normal mice and control subjects. Our results c learly show the existence of an abnormal proteolytic activity of mitoc hondria from patients with DMD on calmitine from the normal mouse. Thi s proteolytic activity was not found on calmitine from the control sub ject. Overall, our observations suggest that calmitine concentration i n the muscle of the control subject remains elevated because of the pr esence of a calmitine-specific protease and an inhibitor of this prote ase which regulates and/or suppresses the activity of the enzyme accor ding to the requirements of the muscle cell. Conversely, the calmitine deficiency observed in the muscle of patients with DMD would be due t o the absence of this inhibitor. This would account for the continual activity of the enzyme in degrading calmitine as soon as it is synthes ized. The identification of this inhibitor is currently being investig ated in OUT laboratory. (C) 1996 Academic Press, Inc.