Abstract
Skeletal muscle is a highly plastic tissue that can alter its metabolic and
contractile features, as well as regenerative potential in response to exercise
and other conditions. Multiple signaling factors including metabolites, kinases,
receptors, and transcriptional factors have been studied in the regulation of
skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have
emerged as a critical transcriptional hub in control of skeletal muscle
homeostasis. ERRα and ERRγ – the two highly expressed
ERR sub-types in the muscle respond to various extracellular cues such as
exercise, hypoxia, fasting and dietary factors, in turn regulating gene
expression in the skeletal muscle. On the other hand, conditions such as
diabetes and muscular dystrophy suppress expression of ERRs in the skeletal
muscle, likely contributing to disease progression. We highlight key functions
of ERRs in the skeletal muscle including the regulation of fiber type,
mitochondrial metabolism, vascularization, and regeneration. We also describe
how ERRs are regulated in the skeletal muscle, and their interaction with
important muscle regulators (e. g. AMPK and PGCs). Finally, we identify
critical gaps in our understanding of ERR signaling in the skeletal muscle, and
suggest future areas of investigation to advance ERRs as potential targets for
function promoting therapeutics in muscle diseases.
Key words
nuclear receptors - transcription - exercise - metabolism - angiogenesis - regeneration
