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. 2020 Jul 5;9(7):1619. doi: 10.3390/cells9071619

Figure 2.

Figure 2

Diagram of the ER stress unfolded protein response (UPR) pathways triggering autophagy. ER stress can activate autophagy through three different UPR branches: EIF2AK3/PERK, ERN/IRE1 and/or the ATF6 signaling pathway. EIF2AK3/PERK induces autophagy by activating the ATG16L1 complex through ATF4 or by inducing DDIT3/CHOP expression, which indirectly causes BECN1 dissociation from BCL2. ERN/IRE1, through MAPK/JNK, mediates the phosphorylation of BCL2, which causes its dissociation from BECN1. The XBP1 branch enhances the formation of LC3-II. The ATF6 pathway also induces autophagy by inhibiting phosphorylation at the AKT-MTOR pathway. Abbreviations: AKT/PKB, AKT serine-threonine kinase; ATF4/6, activating transcription factor 4/6; DDIT3/CHOP/GADD153, DNA damage inducible transcript 3; EIF2AK3/PERK, eukaryotic translation initiation factor 2 alpha kinase 3; ERN/IRE1, endoplasmic reticulum to nucleus signaling 1; MAPK/JNK, mitogen-activated protein kinase and XBP1, X-box binding protein 1.