DOES CALMITINE, A PROTEIN-SPECIFIC FOR THE MITOCHONDRIAL MATRIX OF SKELETAL-MUSCLE, PLAY A KEY ROLE IN MITOCHONDRIAL-FUNCTION

The effect of the myotoxic drug chlorpromazine was studied in vitro on proteins of sarcoplasmic reticulum and mitochondrial matrix of skelet al muscle in the normal mouse. Our results indicate that the drug is s pecific for calcium-binding proteins (calcium ATPase, calsequestrin an d calmitine). Its proteolytic effect on these proteins, apparently due to the stimulation of specific proteases, could account for its myoto xic action. Moreover, calsequestrin (sarcoplasmic reticulum) and calmi tine (mitochondrial matrix) were not sensitive to the same proteases. Proteases acting on calmitine, were inhibited by alpha 2-macroglobulin but not those acting on calsequestrin. Despite some similarities betw een these two proteins, their characteristics of localization and sens itivity of their proteases indicate that calmitine has a specificity w ithin the mitochondrial matrix and very probably plays a major role in the mitochondrial regulation of free calcium, which controls the acti vity of various enzymes of the mitochondrial matrix involved in ATP sy nthesis.