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In this protective role, ATF4 drives the expression of the chaperone heat shock protein family A (Hsp70) member 5 (HSPA5), which in turn stabilizes and enhances the activity of GPX4, thereby inhibiting ferroptotic cell death ( In ferroptosis resistant melanoma cells, CHAC1 was shown to be upregulated by NRF2 independent from ER stress signaling alongside the Aldo-Keto Reductase Family 1 Member C1 (AKR1C1) capable of degrading lipid radicals (Gagliardi et al., 2019)

moreover, Nrf2 was required for cholesterol crystalinduced inflammasome response (107)