Making muscle or mitochondria by selective splicing of PGC-1α

Abstract

Endurance training induces the transcriptional coactivator PGC-1α in skeletal muscle, promoting mitochondrial biogenesis and skeletal muscle remodeling. In a recent issue of Cell, Ruas et al. (2012) show that resistance training regulates the splicing of a novel isoform of PGC-1α (PGC-1α4), which is sufficient to stimulate skeletal muscle hypertrophy.

Figure 1. Regulation and Function of PGC-1α Variants by Exercise in Skeletal Muscle

Endurance training activates the proximal promoter of PGC-1α, whereas resistance exercise stimulates the alternative promoter. Proximal promoter usage and generation of the 1α1 isoform to regulate endurance exercise-dependent skeletal muscle remodeling has been well established. Ruas and colleagues (Ruas et al., 2012) have now proposed a function for a PGC-1α isoform (1α4) during resistance training. Use of the alternative promoter, along with splicing of a premature stop codon between exons 6 and 7, results in 1α4 isoform expression and induction of skeletal muscle hypertrophy.