Fig. 2.

Proposed model of mechanism of action of PGC-1α. PGC-1α is a highly regulated gene that responds to external stimuli, e.g., reduced in diabetes and increased after exercise. When PGC-1α levels rise, the expression of Errα and Gabpa are immediately induced by means of a double-positive-feedback loop. These levels rise, and over the course of 2–3 days, these factors couple with PGC-1α to induce the expression of NRF-1 and hundreds of downstream targets, such as OXPHOS and other mitochondrial genes that are enriched for these transcription factor-binding sites.