Autophagy is activated for cell survival after endoplasmic reticulum stress
Authors
Ogata, MaikoHino, Shin-ichiro
Saito, Atsushi
Morikawa, Keisuke
Kondo, Shinichi
Kanemoto, Soshi
Murakami, Tomohiko
Taniguchi, Manabu
Tanii, Ichiro
Yoshinaga, Kazuya
Shiosaka, Sadao
Hammarback, James A.
Urano, Fumihiko
Imaizumi, Kazunori
Document Type
Journal ArticlePublication Date
2006-10-13Keywords
AutophagyCell Line, Tumor
Cell Survival
Endoplasmic Reticulum
Enzyme Activation
Humans
JNK Mitogen-Activated Protein Kinases
Protein Folding
Signal Transduction
Stress, Physiological
Time Factors
Genetics and Genomics
Metadata
Show full item recordAbstract
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.Source
Mol Cell Biol. 2006 Dec;26(24):9220-31. Epub 2006 Oct 9. Link to article on publisher's siteDOI
10.1128/MCB.01453-06Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43902PubMed ID
17030611Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.01453-06