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. 2020 Aug 17;2020:9738143. doi: 10.1155/2020/9738143

Figure 2.

Figure 2

ER stress retards ferroptosis through the transcription factors ATF4 and Nrf2. Unfolded protein forms misfolded protein via oxidative protein folding (OPF) under excess ROS, initiating ER stress. Under ER stress, the activated sensor protein kinase RNA-like ER kinase (PERK) elicits the unfolded protein response (UPR), inducing transcriptional effects of nuclear factor E2-related factor 2 (Nrf2) and activating transcription factor 4 (ATF4) to resist ferroptosis. The resistant effects benefit from transcriptional production, including the antioxidant response element (ARE), the positive feedback loop related to sequestosome 1 (p62), and the increasing activity and expression of GPX4 related to heat shock protein family A member 5 (HSPA5). Relevant abbreviations: eIF2α: eukaryotic translation initiation factor 2α; KEAP1: Kelch-like ECH-associated protein 1.