HO-1, Nrf2 in Induction of NRF-1 and Mitochondrial Biogenesis!

"endogenous carbon monoxide (CO) generated by HO-1 overexpression stimulates superoxide dismutase-2 upregulation and mitochondrial H2O2 production, which activates Akt/PKB. Akt deactivates glycogen synthase kinase-3β, which permits Nrf2 nuclear translocation and occupancy of 4 antioxidant response elements (AREs) in the NRF-1 promoter. The ensuing accumulation of nuclear NRF-1 protein leads to gene activation for mitochondrial biogenesis,"

Heme Oxygenase-1 Regulates Cardiac Mitochondrial Biogenesis via Nrf2-Mediated Transcriptional Control of Nuclear Respiratory Factor-1 -- Piantadosi et al. 103 (11): 1232 -- Circulation Research:

Role of CO in cardiac mitochondrial biogenesis

"Mitochondrial biogenesis is activated by gene and protein expression of the nuclear respiratory factor 1 (NRF1) and NRF2, of peroxisome proliferator-activated receptor gamma co-activator-1, and of mitochondrial transcription factor A (TFAM), which augmented the copy number of mitochondrial DNA (mtDNA). This is independent of nitric oxide synthase (NOS), as demonstrated by the identical responses in wild-type and endothelial NOS (eNOS)-deficient mice, and by the inhibition of inducible NOS (iNOS)."

A new activating role for CO in cardiac mitochondrial biogenesis -- Suliman et al. 120 (2): 299 -- Journal of Cell Science: