PGC-1 coactivators and skeletal muscle adaptations in health and disease

Abstract

Skeletal muscle adapts to physiological demands by altering a number of programs of gene expression, including those driving mitochondrial biogenesis, angiogenesis, and fiber composition. Recently, the PGC-1 transcriptional coactivators have emerged as key players in the regulation of these adaptations. Many signaling cascades important in muscle physiology impinge directly on PGC-1 expression or activity. In turn, the PGC-1s powerfully activate many of the programs of muscle adaptation. These findings have implications for our understanding of muscle responses to physiological conditions like exercise, as well as in pathological conditions such as cachexia, dystrophy, and peripheral vascular disease.

Figure 1

Schematic of the role of PGC-1α in muscle plasticity. Physiological cues (top) are transduced via key signaling cascades and impinge on the expression of PGC-1α mRNA and the function of PGC-1α protein. In turn, PGC-1α interacts with, and coactivates, a number of transcription factors (examples of which are shown in red), leading to the activation of a number of broad genetic programs (bottom).