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PGC‐1α transfection restores early mitochondrial functional abnormalities in mdx skeletal muscle
Author(s) -
Daussin Frederic Nicolas,
Godin Richard,
Ascah Alexis,
Deschênes Sonia,
Petrof Basil,
Burelle Yan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1051.21
Subject(s) - duchenne muscular dystrophy , mitochondrial biogenesis , electroporation , transfection , mitochondrion , skeletal muscle , microbiology and biotechnology , mitochondrial ros , downregulation and upregulation , biology , oxidative phosphorylation , mitochondrial fusion , myocyte , chemistry , medicine , endocrinology , mitochondrial dna , biochemistry , gene , genetics
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‐1α transfection is beneficial in the mdx mice, a murine model of DMD. Compared to wild‐type, 6 weeks‐old mdx mice exhibited mitochondrial 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‐1α 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 phase of the disease, which were ameliorated 7 days after PGC‐1α 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.