The schematic indicates the upstream signaling events and downstream gene regulatory actions of the inducible PGC-1 coactivators, using PGC-1α as the representative factor. The interaction of PGC-1α with its cognate transcription factor targets is shown linked to specific organ systems. For example, PGC-1α coactivates members of the PPAR nuclear receptor transcription factor family, to activate the expression of genes involved in mitochondrial fatty acid oxidation. The signaling pathways shown at the top of each organ system transduce extracellular physiologic and nutritional stimuli to the expression and/or activity of PGC-1α. LXR, liver X receptor; TAG, triacylglycerol; RXR, retinoid X receptor; mtDNA, mitochondrial DNA; OXPHOS, oxidative phosphorylation.