ER-Phagy: Quality Control and Turnover of Endoplasmic Reticulum

The endoplasmic reticulum (ER) is the largest organelle in cells and has fundamental functions, such as folding, processing, and trafficking of proteins, cellular metabolism, and ion storage. To maintain its function, it is turned over constitutively, and even more actively under certain stress conditions. Quality control of the ER is mediated primarily by two pathways: the ubiquitin-proteasome system and autophagy (termed ‘ER-phagy’). The identification of ER-phagy adaptor molecules has shed light on the mechanisms and physiological significance of ER-phagy. Here, we describe recent findings on various types of ER-phagy and present unanswered questions related to their mechanism and regulation. Lysosomal degradation of the endoplasmic reticulum (ER), which is termed ‘ER-phagy,’ is mediated by macro-ER-phagy, micro-ER-phagy, and the vesicular delivery pathway.ER luminal misfolded proteins can be degraded by not only the proteasome, but also autophagy.Six and two ER-phagy adaptors have been identified in mammals and yeasts, respectively, which differ in their structure, subcellular localization, and tissue distribution.The physiological significance of ER-phagy is under investigation. The ER-phagy adaptor proteins are important for neuronal function and pancreatic homeostasis.ER-phagic flux can be monitored using tandem fluorescent protein-tagged ER reporters.