Pathways involved in cardiac energy metabolism. FA and glucose oxidation are the main ATP-generating pathways in the adult mammalian heart. Acetyl-CoA derived from FA and glucose oxidation is further oxidized in the TCA cycle to generate NADH and FADH₂, which enter the electron transport/oxidative phosphorylation pathway and drive ATP synthesis. Genes encoding enzymes involved at multiple steps of these metabolic pathways (i.e., uptake, esterification, mitochondrial transport,and oxidation) are transcriptionally regulated by PGC-1α with its nuclear receptor partners, including PPARs and ERRs (blue text). Glucose uptake/oxidation and electron transport/oxidative phosphorylation pathways are also regulated by PGC-1α via other transcription factors, such as MEF-2 and NRF-1. Cyt c, cytochrome c.