Mus musculus Transcriptome or Gene expression. Mus musculus

Loss of the co-activators PGC1α/β in skeletal muscle (PKO mice) severely compromises mitochondrial energy metabolism, with muscle damage evident in sedentary mice. Here we show that overexpression of Errγ is sufficient to increase mitochondrial energy metabolism, anti-oxidant defense, angiogenesis, and drive a glycolytic-to-oxidative fiber-type transformation in PKO mice, largely rescuing the muscle damage phenotype. Genomic analyses identify a network of genes directly controlled by ERRγ involved in mitochondrial OXPHOS, TCA cycle, fatty acid oxidation, vasculature development, and fiber-type determination that are regulated independent of PGC1α/β. Notably, the ERRγ-induced metabolic rescue is further boosted by voluntary exercise, suggesting ERRγ as the principal transcriptional partner of PGC1α/β during both innate and exercise-induced oxidative determination.