Molecular Mechanisms of Endoplasmic Reticulum Stress-induced ER-phagy
Endoplasmic reticulum stress(ERS)is a protective cellular response that occurs when cells face hypoxia or nutrient deprivation.It alleviates protein accumulation in the endoplasmic reticulum(ER)by the unfolded protein response.Unfolded or misfolded proteins that are not efficiently cleared by the unfolded protein response pathway are degraded by endoplasmic reticulum-phagy(ER-phagy),which is trigged by ERS to restore ER morphology.ER-phagy is mediated by ER-phagy receptors.In mammali-an and yeast cells,various ER-phagy receptors exist that promote ER fragment formation,capture autoph-agic cargos and deliver them to autolysosomes for degradation.Each ER-phagy receptor has unique struc-tural features that determine its mode of cargo capture.Additionally,ERS regulates ER-phagy by media-ting the expression and phosphorylation of ER-phagy receptors.Research has shown that ERS-induced ER-phagy plays a crucial role in the pathogenesis of various human diseases.Therefore,elucidating the specific mechanisms underlying ERS-induced ER-phagy provides a theoretical basis for the prevention and treatment of ER-phagy-related diseases.Herein,we review the molecular mechanisms of ERS-induced ER-phagy mediated by ER-phagy receptors in mammals(FAM134B,RTN3L,SEC62,CCPG1)and yeasts(Atg39,Atg40,Erp1),as well as the connection between ERS-induced ER-phagy and human diseases such as neurodegenerative disorders and cancer,aiming to provide new strategies for the preven-tion and treatment of ER-phagy-related diseases.
endoplasmic reticulum stress(ERS)endoplasmic reticulum-phagy(ER-phagy)ER-phagy receptorunfolded protein response