Muscular degeneration in Duchenne's dystrophy may be caused by a mitochondrial defect.
Duchenne's dystrophy (DMD), a recessive chromosome X-related disease, is the most common and severe form of myopathy. The different theories (vascular, neurogenic, membraneous, calcic and auto-immune) formulated to account for this disease have not been swept away by the discovery of the DMD gene and the deficient protein, dystrophin, since the exact cellular role played by the latter is still unknown. Our work on skeletal muscle has demonstrated a mitochondrial deficiency of the calcium-specific protein, calmitine, in degenerating muscle of myopathic persons and animals. Considering its great affinity for calcium, this protein specific to skeletal muscle could be essential to mitochondrial calcium regulation and thus to the functioning of the entire muscle cell. Its deficiency in Duchenne's and Becker type muscular dystrophy could be due to a mitochondrial genome alteration solely accountable for muscular degeneration. This hypothesis challenges the supposedly essential but still undefined role that researchers have attributed to dystrophin.
Lucas-Heron
B
B
Laboratoire de Physiologie, UER de Médecine, Nantes, France.
D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency; D002155:Calsequestrin; D004272:DNA, Mitochondrial / Q000235:genetics*; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014960:X Chromosome
C503129:CASQ1 protein, human; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; D004272:DNA, Mitochondrial; D016189:Dystrophin; D024101:Mitochondrial Proteins