Mus musculus Transcriptome or Gene expression

Loss of the co-activators PGC1a/ß in skeletal muscle (PKO mice) severely compromises mitochondrial energy metabolism, with muscle damage evident in sedentary mice. Here we show that overexpression of Err? 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 ERR? involved in mitochondrial OXPHOS, TCA cycle, fatty acid oxidation, vasculature development, and fiber-type determination that are regulated independent of PGC1a/ß. Notably, the ERR?-induced metabolic rescue is further boosted by voluntary exercise, suggesting ERR? as the principal transcriptional partner of PGC1a/ß during both innate and exercise-induced oxidative determination.