Figure 7.

Working diagram of the HO-1/CO/Nrf2 pathway involved in the regulation of mitochondrial biogenesis. Nrf2 constitutively docks with Keap1, which sequesters it in the cytoplasm, allowing it to undergo ubiquitination and degradation (upper left). HO-1/CO increases mitochondrial H₂O₂ (lower left), which stabilizes Keap1 and results in Nrf2 gene expression and nuclear translocation. Nuclear Nrf2 undergoes binding to AREs in the Hmox1, SOD2, and NRF-1 promoters (far right). HO-1 and SOD2 amplify the mitochondrial H₂O₂ signal, whereas NRF-1 entry into the nucleus drives transcription for Tfam, PolRMT, and other genes of mitochondrial biogenesis.