1. Retraction Notice to: Activation of the PPAR/PGC-1α Pathway Prevents a Bioenergetic Deficit and Effectively Improves a Mitochondrial Myopathy Phenotype
- Author
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Francisca P. Díaz, Bruce M. Spiegelman, Carlos T. Moraes, and Tina Wenz
- Subjects
0301 basic medicine ,Bioenergetics ,Physiology ,Cytochrome-c Oxidase Deficiency ,Peroxisome proliferator-activated receptor ,Mice, Inbred Strains ,Mice, Transgenic ,Biology ,Bioinformatics ,Scientific integrity ,Article ,Mice ,03 medical and health sciences ,Adenosine Triphosphate ,Mitochondrial myopathy ,medicine ,Animals ,Transgenes ,Muscle, Skeletal ,Molecular Biology ,chemistry.chemical_classification ,Notice ,Reverse Transcriptase Polymerase Chain Reaction ,Mitochondrial Myopathies ,Cell Biology ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Phenotype ,Mitochondria, Muscle ,PPAR gamma ,Survival Rate ,Blot ,Disease Models, Animal ,030104 developmental biology ,Cell metabolism ,chemistry ,Trans-Activators ,Female ,Bezafibrate ,Energy Metabolism ,Signal Transduction ,Transcription Factors - Abstract
Neuromuscular disorders with defects in the mitochondrial ATP-generating system affect a large number of children and adults worldwide, but remain without treatment. We used a mouse model of mitochondrial myopathy, caused by a cytochrome c oxidase deficiency, to evaluate the effect of induced mitochondrial biogenesis on the course of the disease. Mitochondrial biogenesis was induced either by transgenic expression of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator alpha (PGC-1alpha) in skeletal muscle or by administration of bezafibrate, a PPAR panagonist. Both strategies successfully stimulated residual respiratory capacity in muscle tissue. Mitochondrial proliferation resulted in an enhanced OXPHOS capacity per muscle mass. As a consequence, ATP levels were conserved resulting in a delayed onset of the myopathy and a markedly prolonged life span. Thus, induction of mitochondrial biogenesis through pharmacological or metabolic modulation of the PPAR/PGC-1alpha pathway promises to be an effective therapeutic approach for mitochondrial disorders.
- Published
- 2016