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Diagram of the effects of NRF-1 on the regulation of SDHa- and HIF-1-responsive genes. The loss of NRF-1 leads to loss of catalytic SDHa and depresses Complex II activity, which causes mitochondria to release succinate. Succinate inhibits the PHD, and HIF-1α escapes the Von Hippel-Lindau protein (pVHL) to translocate to the nucleus where it engages with HIF-1β in DNA binding and gene activation. Heme oxygenase-1 (Hmox1, HO-1) is shown as an example of an HIF-1-responsive gene.
