Figure 1.

Mitochondrial biogenesis signalling cascades. Ca²⁺ and AMP/ATP are the main stimuli for mitochondrial biogenesis. Elevated Ca²⁺ and AMP levels activate different kinases that can either phosphorylate CREB to promote PGC-1α expression; or directly phosphorylate PGC-1α leading to its activation. Increased NAD⁺/NADH ratio also results in PGC-1α activation through deacetylation by Sirt1. Once activated, PGC-1α binds to NRF-1/2 to promote expression of several mitochondrial proteins, including TFAM, ultimately resulting in increased mitochondrial biogenesis.