Résumé :
|
We examined the mitochondrial phenotype in skeletal muscle in the early phase of Duchenne muscular dystrophy (DMD), and determined whether upregulation of mitochondrial biogenesis via PGC-1_ transfection is beneficial in the mdx mice, a murine model of DMD. Compared to wild-type, 6 weeks-old mdx mice exhibitedmitochondrial dysfunction including a lower oxidative capacity, a higher susceptibility to Ca2+-induced PTP opening, and an adaptive increase in ROS buffering capacity. Electroporation of the PGC-1_ plasmid largely restored mitochondrial density, as assessed by several marker proteins. Importantly, this translated into an increased mitochondrial Ca2+ buffering capacity and enhanced resistance to PTP opening. Overall, this study reveals several mitochondrial functional abnormalities in the early phaseof the disease, which were ameliorated 7 days after PGC-1_ transfection. In particular, amelioration of mitochondrial Ca2+ buffering capacity may help to improve cellular Ca2+ regulation by limiting the adverse effect of excessive calcium levels, which characterizes DMD.
|