Endoplasmic reticulum quality control by garbage disposal

Various types of intracellular and extracellular stresses disturb homeostasis in the endoplasmic reticulum (ER) and, thus, trigger the ER stress response. Unavoidable and/or prolonged ER stress causes cell toxicity and occasionally cell death. The malfunction or death of irreplaceable cells leads to conformational diseases, including diabetes mellitus, ischemic diseases, metabolic diseases, and neurodegenerative diseases. In the past several decades, many studies have revealed the molecular mechanisms of the ER quality control system. Cells resolve ER stress by promptly and accurately reducing the amount of malfolded proteins. Recent reports have revealed that cells possess several types of ER-related disposal systems, including mRNA decay, proteasomal degradation, and autophagy. The removal of dispensable RNAs, proteins, and organelle parts may enable the effective maintenance of a functional ER. Here, we provide a comprehensive understanding of the ER quality control system by focusing on ER-related garbage disposal systems.