Endoplasmic reticulum stress: cell life and death decisions

The Burnham Institute for Medical Research, La Jolla, California, USA.

Address correspondence to: John C. Reed, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. Phone: (858) 646-3140; Fax: (858) 646-3194; E-mail: gro.mahnrub@eciffodeer.

Abstract

Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged. The mechanisms by which ER stress leads to cell death remain enigmatic, with multiple potential participants described but little clarity about which specific death effectors dominate in particular cellular contexts. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.

Abstract

Acknowledgments

We thank J. Valois for manuscript preparation, M. Hanaii for artwork, and the California Breast Cancer Research Program, the Fondation pour la Recherche Médicale, and the NIH (grants NS047855 and AG15393) for their generous support.

Acknowledgments

Footnotes

Nonstandard abbreviations used: AD, Alzheimer disease; AβP, amyloid β-peptide; DED-L, death effector domain–like; eIF2α, eukaryotic initiation factor 2α; Htt, Huntingtin; IP3, inositol triphosphate; IP3R, IP3 receptor; NOS, nitric oxide synthase; PD, Parkinson disease; PERK, PKR-like ER kinase; polyQ, polyglutamine; PS-1, presenilin-1; SERCA, sarcoplasmic/endoplasmic reticulum Ca^{ATPase; UPR, unfolded protein response; XBP-1, X box protein-1.}

Conflict of interest: The authors have declared that no conflict of interest exists.

Footnotes

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