Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance.
Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance.
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DOI：
10.12688/f1000research.13968.1
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Molinari M
中科院分区：
文献类型：
--
作者：
Fregno I;Molinari M
内质网（ER）是真核细胞中高度动态的细胞器。它与脂质和蛋白质的生物合成、钙的储存以及各种外源性和内源性有害化合物的解毒有关。ER活性和大小必须迅速适应环境和发育条件或生物合成需求。这是通过诱导被定义为“未折叠蛋白反应”的经过深入研究的转录/翻译程序来实现的，所述转录/翻译程序增加ER体积和调节众多ER功能的ER驻留蛋白的表达。不太了解的是溶酶体分解代谢过程，其维持ER大小处于稳态，防止ER应激期间ER过度扩张，或确保从ER应激恢复期间恢复到生理ER大小。这些分解代谢过程也可能被激活，以消除ER亚结构域，其中蛋白酶体抗性错误折叠蛋白或受损脂质已被分离。对这些分解代谢机制的见解最近才随着所谓的ER-吞噬受体的鉴定而出现，ER-吞噬受体标记特定的ER亚结构域用于选择性溶酶体递送以进行清除。在这里，在八个章节和一个附录，我们评论的ER周转途径的最新进展引起的ER压力，营养剥夺，错误折叠的蛋白质，和活细菌。我们强调酵母（Atg 39和Atg 40）和哺乳动物（FAM 134 B，SEC 62，RTN 3和CCPG 1）ER-吞噬受体和自噬基因在选择性和非选择性分解代谢过程中的作用，通过控制ER的大小，营业额和功能来调节细胞蛋白质稳态。
The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied transcriptional/translational programs defined as “unfolded protein responses” that increase the ER volume and the expression of ER-resident proteins regulating the numerous ER functions. Less understood are the lysosomal catabolic processes that maintain ER size at steady state, that prevent excessive ER expansion during ER stresses, or that ensure return to physiologic ER size during recovery from ER stresses. These catabolic processes may also be activated to remove ER subdomains where proteasome-resistant misfolded proteins or damaged lipids have been segregated. Insights into these catabolic mechanisms have only recently emerged with the identification of so-called ER-phagy receptors, which label specific ER subdomains for selective lysosomal delivery for clearance. Here, in eight chapters and one addendum, we comment on recent advances in ER turnover pathways induced by ER stress, nutrient deprivation, misfolded proteins, and live bacteria. We highlight the role of yeast (Atg39 and Atg40) and mammalian (FAM134B, SEC62, RTN3, and CCPG1) ER-phagy receptors and of autophagy genes in selective and non-selective catabolic processes that regulate cellular proteostasis by controlling ER size, turnover, and function.