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. 2022 Oct 4;11(19):3123. doi: 10.3390/cells11193123

Figure 1.

Figure 1

Pathways for intracellular oxygen/redox status sensing by HIF-1/2 and Nrf2. (A) Low O2 levels reduce the rate of HIF-1/2α hydroxylation, which leads to molecular recognition by the Von Hippel-Lindau tumor suppressor protein (pVHL) and subsequent proteasomal degradation. Stabilized HIF-1/2α binds HIF-β and translocates to the nucleus, where it binds the hypoxia response element (HRE) in DNA, inducing expression of glycolytic, proliferative, and pro-survival genes, among others. (B) High O2 levels promote increased reactive oxygen species (ROS) production. ROS-mediated oxidation of Keap1 releases Nrf2 preventing its proteasomal degradation. Nrf2 then translocates to the nucleus, heterodimerizes with small musculo-aponeurotic fibrosarcoma (sMaf), and binds to the antioxidant response element (ARE), inducing expression of genes involved in ROS and xenobiotic detoxification. Created with BioRender.com (accessed on 14 July 2022).