Endoplasmic reticulum autophagy in inflammatory diseases

Abstract

The endoplasmic reticulum (ER) is responsible for the synthesis, modification, and folding of various intracellular proteins. Under strong external stimuli, the ER often undergoes significant structural disorganization and functional abnormalities, a process that generally accelerates the onset and progression of inflammatory responses and related diseases, such as infections and sepsis, digestive system diseases, cancer, neurological disorders, circulatory diseases, and musculoskeletal diseases. Therefore, maintaining ER homeostasis is crucial for delaying the inflammatory process. As an important type of selective autophagy, ER-phagy has transcended merely “waste removal” to become a key cellular hub integrating immune and stress signals. It not only effectively curbs the excessive activation of the NF-κB pathway and the NLRP3 inflammasome by timely clearing inflammatory pathogens and ER fragments damaged by calcium store abnormalities and oxidation but also maintains immune cell homeostasis, thereby inhibiting the initiation and spread of excessive inflammatory responses. This review summarizes the key receptors, regulatory mechanisms, and the latest research on ER-phagy in various inflammation-related diseases, aiming to draw academic attention to the important value of ER-phagy in inflammatory diseases.