Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery
Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery
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DOI：
10.1038/ncb3423
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发表时间：
2016-11-01
影响因子：
21.3
通讯作者：
Molinari, Maurizio
中科院分区：
文献类型：
--
作者：
Fumagalli, Fiorenza;Noack, Julia;Molinari, Maurizio
内质网（ER）是真核细胞中蛋白质生物合成的场所。扰乱ER稳态激活统称为未折叠蛋白反应（UPR）的应激程序。UPR增强ER驻留分子伴侣和酶的产生，以减少错误折叠蛋白质的负担。在ER应激的解决上，不明确的、选择性的自噬程序去除多余的ER组分。在这里，我们确定Sec 62，在哺乳动物ER的转运子复合物调节蛋白进口的组成部分，作为ER居民自噬受体。Sec 62在从ER应激恢复期间进行干预，以选择性地将ER组分递送至自体溶酶体系统，以在我们命名为恢复-吞噬的一系列事件中进行清除。Sec 62在C-末端胞质结构域中含有保守的LC 3相互作用区域，其在回收吞噬中的功能是必需的，但在蛋白质易位机制中的功能是不确定的。我们的研究结果确定Sec 62作为维持和恢复ER稳态的关键分子组分。
The endoplasmic reticulum (ER) is a site of protein biogenesis in eukaryotic cells. Perturbing ER homeostasis activates stress programs collectively called the unfolded protein response (UPR). The UPR enhances production of ER-resident chaperones and enzymes to reduce the burden of misfolded proteins. On resolution of ER stress, ill-defined, selective autophagic programs remove excess ER components. Here we identify Sec62, a constituent of the translocon complex regulating protein import in the mammalian ER, as an ER-resident autophagy receptor. Sec62 intervenes during recovery from ER stress to selectively deliver ER components to the autolysosomal system for clearance in a series of events that we name recovER-phagy. Sec62 contains a conserved LC3-interacting region in the C-terminal cytosolic domain that is required for its function in recovER-phagy, but is dispensable for its function in the protein translocation machinery. Our results identify Sec62 as a critical molecular component in maintenance and recovery of ER homeostasis.