Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland; School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Dev Cell. 2021 Apr 5;56(7):949-966. doi: 10.1016/j.devcel.2021.03.005. Epub 2021 Mar 24.
ER-phagy, literally endoplasmic reticulum (ER)-eating, defines the constitutive or regulated clearance of ER portions within metazoan endolysosomes or yeast and plant vacuoles. The advent of electron microscopy led to the first observations of ER-phagy over 60 years ago, but only recently, with the discovery of a set of regulatory proteins named ER-phagy receptors, has it been dissected mechanistically. ER-phagy receptors are activated by a variety of pleiotropic and ER-centric stimuli. They promote ER fragmentation and engage luminal, membrane-bound, and cytosolic factors, eventually driving lysosomal clearance of select ER domains along with their content. After short historical notes, this review introduces the concept of ER-phagy responses (ERPRs). ERPRs ensure lysosomal clearance of ER portions expendable during nutrient shortage, nonfunctional, present in excess, or containing misfolded proteins. They cooperate with unfolded protein responses (UPRs) and with ER-associated degradation (ERAD) in determining ER size, function, and homeostasis.
ER 噬作用，字面意思是内质网（ER）的吞噬，定义了真核生物内溶酶体或酵母和植物液泡中 ER 部分的组成型或受调控的清除。电子显微镜的出现导致了 60 多年前对 ER 噬作用的首次观察，但直到最近，随着一组名为 ER 噬作用受体的调节蛋白的发现，其机制才得以阐明。ER 噬作用受体被多种多效性和 ER 中心刺激激活。它们促进 ER 片段化，并参与腔、膜结合和细胞质因子，最终沿着它们的内容物驱动溶酶体清除选择的 ER 结构域。在简短的历史注释之后，本综述介绍了 ER 噬作用反应（ERPR）的概念。ERPR 确保在营养缺乏、功能失调、过量存在或含有错误折叠蛋白时，溶酶体清除可消耗的 ER 部分。它们与未折叠蛋白反应（UPR）和 ER 相关降解（ERAD）合作，以确定 ER 的大小、功能和动态平衡。
