title: Autophagy is activated for cell survival after endoplasmic reticulum stress.
abstract: 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.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Ogata
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Hino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Keisuke
authors.initials: K
authors.lastname: Morikawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kondo
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Manabu
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanii
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Sadao
authors.initials: S
authors.lastname: Shiosaka
authors.forename: James A
authors.initials: JA
authors.lastname: Hammarback
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D017510:Protein Folding; D015398:Signal Transduction; D013312:Stress, Physiological / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases