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 skeletal muscle in the normal mouse. Our results indicate that the drug is specific for calcium-binding proteins (calcium ATPase, calsequestrin and calmitine). Its proteolytic effect on these proteins, apparently due to the stimulation of specific proteases, could account for its myotoxic action. Moreover, calsequestrin (sarcoplasmic reticulum) and calmitine (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 between these two proteins, their characteristics of localization and sensitivity of their proteases indicate that calmitine has a specificity within the mitochondrial matrix and very probably plays a major role in the mitochondrial regulation of free calcium, which controls the activity of various enzymes of the mitochondrial matrix involved in ATP synthesis.
Lucas-Heron
B
B
Laboratoire de Physiologie, Faculté de Médecine, Nantes, France.
Le Ray
B
B
Schmitt
N
N
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002155:Calsequestrin / Q000037:antagonists & inhibitors / Q000502:physiology; D002746:Chlorpromazine / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology*; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure
D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; D010450:Endopeptidases; D000252:Calcium-Transporting ATPases; D002746:Chlorpromazine