Autophagy is activated for cell survival after endoplasmic reticulum stress
Autophagy is activated for cell survival after endoplasmic reticulum stress
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DOI：
10.1128/mcb.01453-06
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发表时间：
2006-12-01
影响因子：
5.3
通讯作者：
Imaizumi, Kazunori
中科院分区：
文献类型：
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作者：
Ogata, Maiko;Hino, Shin-ichiro;Imaizumi, Kazunori
真核细胞通过未折叠蛋白反应处理未折叠蛋白在内质网（ER）中的积累，包括诱导分子伴侣、翻译衰减和ER相关降解，以防止细胞死亡。在这里，我们发现自噬系统被激活作为一种新的信号通路，在响应ER应激。用ER应激物处理SK-N-SH神经母细胞瘤细胞，显著诱导自噬体的形成，这在超微结构水平上被识别。绿色荧光蛋白（GFP）-LC 3标记的结构（GFP-LC 3“点”）的形成，代表自噬体，在暴露于ER应激的细胞中被广泛诱导，从LC 3-I转化为LC 3-II。在IRE 1缺陷细胞或用c-Jun N-末端激酶（JNK）抑制剂处理的细胞中，ER应激诱导的自噬被抑制，表明ER应激后自噬激活需要IRE 1-JNK通路。相比之下，PERK缺陷细胞和ATF 6敲低细胞显示ER应激后以类似于野生型细胞的方式诱导自噬。自噬的紊乱使细胞易受内质网应激的影响，表明自噬在内质网应激后的细胞存活中起重要作用。
Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress.