Endoplasmic Reticulum Stress Triggers Autophagy

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2006 Aug 12

PMID 16901900

Citations 474

Authors

Tomohiro Yorimitsu

Usha Nair

Zhifen Yang

Daniel J Klionsky

Affiliations

Soon will be listed here.

Abstract

Eukaryotic cells have evolved strategies to respond to stress conditions. For example, autophagy in yeast is primarily a response to the stress of nutrient limitation. Autophagy is a catabolic process for the degradation and recycling of cytosolic, long lived, or aggregated proteins and excess or defective organelles. In this study, we demonstrate a new pathway for the induction of autophagy. In the endoplasmic reticulum (ER), accumulation of misfolded proteins causes stress and activates the unfolded protein response to induce the expression of chaperones and proteins involved in the recovery process. ER stress stimulated the assembly of the pre-autophagosomal structure. In addition, autophagosome formation and transport to the vacuole were stimulated in an Atg protein-dependent manner. Finally, Atg1 kinase activity reflects both the nutritional status and autophagic state of the cell; starvation-induced autophagy results in increased Atg1 kinase activity. We found that Atg1 had high kinase activity during ER stress-induced autophagy. Together, these results indicate that ER stress can induce an autophagic response.

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References

Patil C, Walter P . Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol. 2001; 13(3):349-55. DOI: 10.1016/s0955-0674(00)00219-2. View

Kim J, Kamada Y, Stromhaug P, Guan J, Baba M, Scott S . Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole. J Cell Biol. 2001; 153(2):381-96. PMC: 2169458. DOI: 10.1083/jcb.153.2.381. View

Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y . The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 2001; 20(21):5971-81. PMC: 125692. DOI: 10.1093/emboj/20.21.5971. View

Ishihara N, Hamasaki M, Yokota S, Suzuki K, Kamada Y, Kihara A . Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell. 2001; 12(11):3690-702. PMC: 60286. DOI: 10.1091/mbc.12.11.3690. View

Kim J, Huang W, Stromhaug P, Klionsky D . Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation. J Biol Chem. 2001; 277(1):763-73. PMC: 2754695. DOI: 10.1074/jbc.M109134200. View

Shintani T, Huang W, Stromhaug P, Klionsky D . Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. Dev Cell. 2002; 3(6):825-37. PMC: 2737732. DOI: 10.1016/s1534-5807(02)00373-8. View

Abeliovich H, Zhang C, Dunn Jr W, Shokat K, Klionsky D . Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy. Mol Biol Cell. 2003; 14(2):477-90. PMC: 149986. DOI: 10.1091/mbc.e02-07-0413. View

Hamasaki M, Noda T, Ohsumi Y . The early secretory pathway contributes to autophagy in yeast. Cell Struct Funct. 2003; 28(1):49-54. DOI: 10.1247/csf.28.49. View

Kostova Z, Wolf D . For whom the bell tolls: protein quality control of the endoplasmic reticulum and the ubiquitin-proteasome connection. EMBO J. 2003; 22(10):2309-17. PMC: 155985. DOI: 10.1093/emboj/cdg227. View

10.

Spear E, Ng D . Stress tolerance of misfolded carboxypeptidase Y requires maintenance of protein trafficking and degradative pathways. Mol Biol Cell. 2003; 14(7):2756-67. PMC: 165674. DOI: 10.1091/mbc.e02-11-0717. View

11.

Klionsky D, Cregg J, Dunn Jr W, Emr S, Sakai Y, Sandoval I . A unified nomenclature for yeast autophagy-related genes. Dev Cell. 2003; 5(4):539-45. DOI: 10.1016/s1534-5807(03)00296-x. View

12.

Levine B, Klionsky D . Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004; 6(4):463-77. DOI: 10.1016/s1534-5807(04)00099-1. View

13.

Reggiori F, Wang C, Nair U, Shintani T, Abeliovich H, Klionsky D . Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae. Mol Biol Cell. 2004; 15(5):2189-204. PMC: 404015. DOI: 10.1091/mbc.e03-07-0479. View

14.

Ravikumar B, Vacher C, Berger Z, Davies J, Luo S, Oroz L . Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004; 36(6):585-95. DOI: 10.1038/ng1362. View

15.

Shintani T, Klionsky D . Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. J Biol Chem. 2004; 279(29):29889-94. PMC: 1712665. DOI: 10.1074/jbc.M404399200. View

16.

Cuervo A, Stefanis L, Fredenburg R, Lansbury P, Sulzer D . Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 2004; 305(5688):1292-5. DOI: 10.1126/science.1101738. View

17.

Robinson J, Klionsky D, Banta L, Emr S . Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol. 1988; 8(11):4936-48. PMC: 365587. DOI: 10.1128/mcb.8.11.4936-4948.1988. View

18.

Normington K, Kohno K, Kozutsumi Y, Gething M, Sambrook J . S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP. Cell. 1989; 57(7):1223-36. DOI: 10.1016/0092-8674(89)90059-7. View

19.

Klionsky D, Cueva R, Yaver D . Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. J Cell Biol. 1992; 119(2):287-99. PMC: 2289658. DOI: 10.1083/jcb.119.2.287. View

20.

Kamada Y, Jung U, Piotrowski J, Levin D . The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response. Genes Dev. 1995; 9(13):1559-71. DOI: 10.1101/gad.9.13.1559. View