The PPARGC1A gene is transcribed to yield mRNA and the mRNA is translated to yield PPARGC1A protein (Larrouy et al. 1999, Knutti et al. 2000, Pilegaard et al. 2003). PPARGC1A protein is located in the nucleus where it coactivates transcription. As inferred from mouse homologs in liver (Herzig et al. 2001) and brown adipose tissue (Cao et al. 2004), phosphorylated CREB enhances expression of PPARGC1A (PGC-1alpha) (Handschin et al. 2003, Yoshioka et al. 2009). CRTC proteins (TORC proteins) coactivate the activation by CREB (Wu et al. 2006). CREB is phosphorylated in response to cAMP As inferred from mouse, phosphorylated ATF2 binds the PGC-1alpha promoter and enhances expression (Cao et al. 2004, Akimoto et al. 2005, Wright et al. 2007, Akimoto et al. 2008). Intracellular calcium acting via p38 MAPK is believed to activate (phosphorylate) ATF2. As inferred from mouse, MEF2C or MEF2D with PGC-1alpha activate expression of PGC-1alpha (Handschin et al. 2003). NR1D1 (REV-ERBA) binds heme and the promoter of the PGC-1alpha (PPARGC1A) gene. The REV-ERBA:heme complex recruits the corepressors NCoR and HDAC3 and represses transcription. PGC-1alpha (PPARGC1A) enhances expression of its own gene in mouse (Jager et al.2007) and in rat hepatocytes (Lin et al. 2003)