FIGURE 2.

NRF2 is involved in the regulation of ferroptosis. Under normal conditions, NRF2 is degraded by the Keap1-CUL3-RBX1 E3 ubiquitin ligase complex-targeted proteasome. Under oxidative stress conditions, NRF2 is no longer degraded, thus allowing nuclear translocation and binding to the ARE. NRF2 promotes G6PD expression to increases NADPH via the pentose phosphate pathway, GSH and TXN production is dependent on NADPH, which promotes CoQ10 production. NRF2 promotes the expression of SLC7A11, GCLC, GCLM, GSS to increase GSH synthesis, and NRF2 also promotes the expression of GPX4. GPX4 converts GSH to GSSG to reduce lipid hydrogen peroxide. NRF2 can promote the expression of ferritin and FPN to store Fe²⁺ and excrete Fe²⁺ respectively, and reduce Fe²⁺ in LIP; Nrf2 also promote the expression of HO-1.