Università della Svizzera italiana, Lugano, Switzerland.
Institute for Research in Biomedicine, Bellinzona, Switzerland.
Prog Mol Subcell Biol. 2021;59:99-114. doi: 10.1007/978-3-030-67696-4_5.
The endoplasmic reticulum (ER) is a biosynthetic organelle in eukaryotic cells. Its capacity to produce proteins, lipids and oligosaccharides responds to physiologic and pathologic demand. The transcriptional and translational unfolded protein response (UPR) programs increase ER size and activity. In contrast, ER-phagy programs in all their flavors select ER subdomains for lysosomal clearance. These programs are activated by nutrient deprivation, accumulation of excess ER (recov-ER-phagy), production of misfolded proteins that cannot be degraded by ER-associated degradation and that are removed from cells by the so-called ER-to-lysosome-associated degradation (ERLAD). Selection of ER subdomains to be cleared from cells relies on ER-phagy receptors, a class of membrane-bound proteins displaying cytosolic domains that engage the cytosolic ubiquitin-like protein LC3. Mechanistically, ER clearance proceeds via macro-ER-phagy, micro-ER-phagy and LC3-regulated vesicular delivery.
内质网（ER）是真核细胞中的一种生物合成细胞器。它产生蛋白质、脂质和寡糖的能力响应生理和病理需求。转录和翻译未折叠蛋白反应（UPR）程序增加 ER 的大小和活性。相比之下，各种形式的 ER 自噬程序选择 ER 亚区进行溶酶体清除。这些程序由营养剥夺、过量 ER 的积累（再 ER-自噬）、不能被 ER 相关降解降解的错误折叠蛋白质的产生以及所谓的 ER 到溶酶体相关降解（ERLAD）而被细胞清除所激活。从细胞中清除 ER 亚区的选择依赖于 ER 自噬受体，这是一类具有细胞质结构域的膜结合蛋白，与细胞质泛素样蛋白 LC3 结合。从机制上讲，ER 清除通过大 ER-自噬、微 ER-自噬和 LC3 调节的囊泡递送来进行。
