The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family includes ligands of multiple nuclear or non-nuclear receptors that control the expression of specific genes regulating cell metabolism. The first discovered member of the PGC-1 family, a 91 kDa nuclear protein identified in brown adipose tissue (BAT) in mouse studies of cold-induced thermogenesis, was called peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α). The biological activity of PGC-1α is tightly controlled at several levels: by transcriptional control (of multiple promoter regions), alternative splicing of transcripts, and post-translational modification (e.g., phosphorylation, acetylation, or methylation). 
As a transcription factor, PGC-1α can bind to targets such as PPARα, PPARβ/δ, and PPARγ, which coordinate the expression of mitochondrial genes and indirectly contribute to fatty acid (FA) transport and utilization. Furthermore, PGC-1α upregulates the expression of several genes of the tricarboxylic acid cycle  and the mitochondrial FA oxidation pathway. PGC-1α also regulates the expression of nuclear and mitochondrial genes that encode components of the electron transport system and oxidative phosphorylation (OXPHOS) via nuclear respiratory factors 1 and 2 (NRF-1 and -2) and estrogen-related receptor α (ERRα) coactivation.  β-adrenergic stimulation of a PGC-1 α/estrogen-related receptor alpha (ERRα)/vascular endothelial growth factor (VEGF) axis modulates exercise-induced angiogenesis in skeletal muscle and truncated PGC-1α can lead to hypoxic induction of VEGF and angiogenesis in skeletal muscle. Several myokines are regulated by PGC-1: irisin/FNDC5, myostatin, and BDNF. Irisin stimulates glucose uptake and lipid metabolism via the activation of AMP-activated protein kinase (AMPK) [28,29,30] and is also involved in muscle growth by inducing insulin-like growth factor 1 and suppressing myostatin. In addition to having effects on muscle, exogenous administration of irisin induces adipocyte browning in subcutaneous fat in mice via p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2).


1.Ching-Feng Cheng,et al. Int J Mol Sci. 2018 Nov; 19(11): 3447.