Autophagy is activated for cell survival after endoplasmic reticulum stress

Maiko Ogata, Shin Ichiro Hino, Atsushi Saito, Keisuke Morikawa, Shinichi Kondo, Soshi Kanemoto, Tomohiko Murakami, Manabu Taniguchi, Ichiro Tanii, Kazuya Yoshinaga, Sadao Shiosaka, James A. Hammarback, Fumihiko Urano, Kazunori Imaizumi

Research output: Contribution to journalArticlepeer-review

1426 Scopus citations

Abstract

Eukaryotic cells deal with accumulation of unfolded proteins in the eedoplasmic 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.

Original languageEnglish
Pages (from-to)9220-9231
Number of pages12
JournalMolecular and cellular biology
Volume26
Issue number24
DOIs
StatePublished - Dec 2006

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