Activation of the PPAR/PGC-1α Pathway Prevents a Bioenergetic Deficit and Effectively Improves a Mitochondrial Myopathy Phenotype

Tina Wenz, Francisca Diaz, Bruce M. Spiegelman, Carlos T. Moraes

Research output: Contribution to journalArticle

258 Scopus citations


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 γ (PPARγ) coactivator α (PGC-1α) 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-1α pathway promises to be an effective therapeutic approach for mitochondrial disorders.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalCell Metabolism
Issue number3
StatePublished - Sep 3 2008




ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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