Endoplasmic Reticulum Stress and Autophagy

Abstract

In 1945, K. R. Porter et al. observed mouse embryonic fibroblasts (MEFs) and found that the cytoplasmic part of the cell had an unreported reticular structure, so it was named endoplasmic reticulum (ER). The major functions of the endoplasmic reticulum are: synthesis of intracellular proteins and the modification and processing of proteins. It is an important organelle in eukaryotic cells. It is a three-dimensional network structure in which complex and closed intracellular tubular intimal systems are intertwined. When cells are subjected to various strong stimulating factors such as nutrient deficiencies, Ca²⁺ metabolic imbalance, toxin stimulation, and sustained oxidative stress stimulation, the cell homeostasis will be broken. In order to survive, a series of cell self-protection event will be initiated including the endoplasmic reticulum stress (ERS). The UPR can further promote the expression of the proteins which can help the misfolded and unfolded proteins restore to its normal structure through the activation of PERK, IRE1, and ATF6. However, the co-working of UPR and the ubiquitin-proteasome system still cannot make the endoplasmic reticulum restoring to its normal state, when the stimuli persist or are too strong. The damaged endoplasmic reticulum can be partially engulfed by the autophagic vesicles for degradation when the ERS persists. The degraded endoplasmic reticulum fragments can be reassembled into a new endoplasmic reticulum to restore the normal state of it. Hence, it seems that the autophagy has become the last mean to restore the homeostasis of endoplasmic reticulum.