Muscular dystrophy: possible role of mitochondrial deficiency in muscle degeneration processes.
We isolated mitochondria from fast-twitch (extensor digitorum longus) and slow-twitch (soleus) skeletal muscle of the adult rat in normal conditions and 45 days after denervation as well as from skeletal muscle (gastrocnemius) of control and dystrophic (C57BL6J dy/dy and mdx) mice. We searched for the presence of a calcium-specific mitochondrial protein (calmitine) and measured calcium uptake in mitochondria. Our results indicate a possible correlation between the quantity of calmitine present and calcium entry into mitochondria. Both these parameters were elevated in rat fast-twitch and mouse mixed muscle and very low in slow-twitch muscle. They were also very low in dystrophic mouse muscle (C57BL6J dy/dy) with extensive muscle degeneration, but on the contrary elevated in muscle (mdx) with no important signs of degeneration. Finally, we found a normal calmitine concentration and very low calcium uptake in rat extensor digitorum longus after 45 days of denervation. On the basis of these results, it is hypothesized that calmitine synthesis could be subject to neural influence, thus specific for fast-twitch muscle, and that it could be linked to mitochondrial calcium uptake. A decrease in uptake could disturb certain enzymatic activities related to ATP synthesis and bring about muscle degeneration by inhibiting such synthesis. This would occur in the context of reduced calmitine synthesis in the case of genetic anomalies and of inactivation of calmitine after neural disturbance in the case of denervation.
Lucas-Heron
B
B
Laboratoire de Physiologie, UER de Médecine et Unité de Recherche CNRS 1340, Nantes, France.
Schmitt
N
N
Ollivier
B
B
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002155:Calsequestrin; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; D002118:Calcium