Crosstalk of ER stress‐mediated autophagy and ER‐phagy: Involvement of UPR and the core autophagy machinery

Abstract

Endoplasmic reticulum (ER) stress, a common cellular stress response, is closely related to the activation of autophagy that is an important and evolutionarily conserved mechanism for maintaining cellular homeostasis. Autophagy induced by ER stress mainly includes the ER stress-mediated autophagy and ER-phagy. The ER stress-mediated autophagy is characterized by the generation of autophagosomes that include worn-out proteins, protein aggregates, and damaged organelles. While the autophagosomes of ER-phagy selectively include ER membranes, and the double membranes also derive, at least in part, from the ER. The signaling pathways of IRE1α, PERK, ATF6, and Ca are necessary for the activation of ER stress-mediated autophagy, while the receptor-mediated selective ER-phagy degrades the ER is Atg40/FAM134B. The ER stress-mediated autophagy and ER-phagy not only have differences, but also have connections. The activation of ER-phagy requires the core autophagy machinery, and the ER-phagy may be a branch of ER stress-mediated autophagy that selectively targets the ER. However, the determined factors that control the changeover switch between ER stress-mediated autophagy and ER-phagy are largely obscure, which may be associated with the type of cells and the extent of stimulation. This review summarized the crosstalk between ER stress-mediated autophagy and ER-phagy and their signaling networks. Additionally, we discussed the possible factors that influence the type of autophagy induced by ER stress.

Autophagy May Protect Against Parenteral Nutrition‐Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress

“…Rapamycin treatment also downregulated cleaved‐caspase3 expression (Figure ) and upregulated BCL2 expression (Figure S2). Activation of ER stress can induce autophagy . However, there is evidence that autophagy modulation affects ER stress .…”

STING Senses Microbial Viability to Orchestrate Stress-Mediated Autophagy of the Endoplasmic Reticulum

“…The unfolded protein response in yeast triggers autophagy-dependent removal of ER membranes, a process termed ER-phagy (Bernales et al, 2007). The ER-phagy triggered by live Gram-positive bacteria is distinct from the yeast ER-phagy pathway that operates independently of canonical autophagy (Bernales et al, 2007; Schuck et al, 2014), and is likely a branch of ER-stress mediated autophagy that targets the ER (Song et al, 2017). The spectrum of molecules involved in different forms of ER-phagy is not known.…”

Intermittent-Hypoxia-Induced Autophagy Activation Through the ER-Stress-Related PERK/eIF2α/ATF4 Pathway is a Protective Response to Pancreatic β-Cell Apoptosis

“…In those studies, TUDCA or 4-PBA was commonly used for inhibiting ER stress [35,36]. Recently, some studies have discovered that ER stress also induces ERphagy, a new branch of macroautophagy that involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER [37,38]. However, in this study, the type of autophagy induced by ER stress is still unclear and needs further study.…”

“…The UPR is characterized by three major canonical branches: inositol-requiring protein-1α, PERK, and ATF6, which have been demonstrated to regulate autophagy at different stages in the process [37,41,42].…”