First Author | Fan W | Year | 2018 |
Journal | Cell Rep | Volume | 22 |
Issue | 10 | Pages | 2521-2529 |
PubMed ID | 29514081 | Mgi Jnum | J:271001 |
Mgi Id | MGI:6278369 | Doi | 10.1016/j.celrep.2018.02.047 |
Citation | Fan W, et al. (2018) ERRgamma Promotes Angiogenesis, Mitochondrial Biogenesis, and Oxidative Remodeling in PGC1alpha/beta-Deficient Muscle. Cell Rep 22(10):2521-2529 |
abstractText | PGC1alpha is a pleiotropic co-factor that affects angiogenesis, mitochondrial biogenesis, and oxidative muscle remodeling via its association with multiple transcription factors, including the master oxidative nuclear receptor ERRgamma. To decipher their epistatic relationship, we explored ERRgamma gain of function in muscle-specific PGC1alpha/beta double-knockout (PKO) mice. ERRgamma-driven transcriptional reprogramming largely rescues muscle damage and improves muscle function in PKO mice, inducing mitochondrial biogenesis, antioxidant defense, angiogenesis, and a glycolytic-to-oxidative fiber-type transformation independent of PGC1alpha/beta. Furthermore, in combination with voluntary exercise, ERRgamma gain of function largely restores mitochondrial energetic deficits in PKO muscle, resulting in a 5-fold increase in running performance. Thus, while PGC1s can interact with multiple transcription factors, these findings implicate ERRs as the major molecular target through which PGC1alpha/beta regulates both innate and adaptive energy metabolism. |