Nrf2 activation depends on NAD status

Found an indirect dependency of Nrf2 activation from Vitamin B3 status (NAD+):

BACH1 is a competitive inhibitor of Nrf2. It competes with Nrf2 transcription factor by binding to small Maf proteins and to ARE (antioxidant response elements on DNA), preventing Nrf2 from binding to them. (R1)

Turns out, Sirtuin 6 facilitates detachment of BACH1 from ARE, thus freeing the “zone” for Nrf2. (R2)

And as we know, sirtuins are NAD dependent deacetylases. (R3)

Therefore: low NAD level reduces Nrf2 activation.

References

1
Bach1: Function, Regulation, and Involvement in Disease
2018
2
Hepatocyte-specific sirtuin 6 deletion predisposes to nonalcoholic steatohepatitis by up-regulation of Bach1, an Nrf2 repressor
2017
3
Sirtuin 6 (wikipedia)