Fig. (1).

Overview of mitochondrial biogenesis in neurons. PGC-1α/NRF-1/2/TFAM is the main regulatory pathway of mitochondrial biogenesis. Activated PGC-1α stimulates nuclear transcription factors NRF-1, NRF-2, ERR‐α and the final effector TFAM, which (along with TFB1M, and TFB2M) controls mtDNA transcription and replication. Increased AMP/ATP ratio triggers the PGC-1α/NRF-1/2/TFAM pathway via AMPK activation, which in turn phosphorylates PGC-1α. Elevated Ca²⁺ levels induce mitochondrial biogenesis via CaMK activation, CaMK phosphorylates p38-MAPK, activating PGC-1α. Increased NAD+/NADH ratio induces mitochondrial biogenesis via SIRT1 activation, deacetylating PGC-1α. Dashed lines are for translocation.