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. Author manuscript; available in PMC: 2024 Feb 1.
Published in final edited form as: Hepatology. 2022 May 24;77(2):619–639. doi: 10.1002/hep.32562

Fig. 2. Severe ER Stress Triggers Maladaptive UPR.

Fig. 2.

Severe ER stress triggers maladaptive UPR, leading to activation of cell death. Hyperactivated PERK triggers overexpression of NFE2L2-/ATF4-target genes leading to excessive autophagy, cell death, and CHOP-mediated apoptosis. Also, hyperactivation of IRE1 induces apoptosis via CASP2 activation. Hyperactivated MAPK8 and XBP1s induce overexpression of autophagy genes, resulting in excessive autophagy. Similarly, hyperactivation of ATF6α induces overexpression of proapoptotic factors and autophagy genes, ultimately, leading to cell death (5).