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Journal of Cell Communication and Signaling

, Volume 8, Issue 4, pp 311–321 | Cite as

Getting the better of ER stress

  • Bertrand Mollereau
  • Serge Manié
  • Francesco Napoletano
RESEARCH ARTICLE

Abstract

Research over the past few years has highlighted the ability of the unfolded protein response (UPR) to minimize the deleterious effects of accumulated misfolded proteins under both physiological and pathological conditions. The endoplasmic reticulum (ER) adapts to endogenous and exogenous stressors by expanding its protein-folding capacity and by stimulating protective processes such as autophagy and antioxidant responses. Although it is clear that severe ER stress can elicit cell death, several recent studies have shown that low levels of ER stress may actually be beneficial to cells by eliciting an adaptive UPR that ‘preconditions’ the cell to a subsequent lethal insult; this process is called ER hormesis. The findings have important implications for the treatment of a wide variety of diseases associated with defective proteostasis, including neurodegenerative diseases, diabetes, and cancer. Here, we review the physiological and pathological functions of the ER, with a particular focus on the molecular mechanisms that lead to ER hormesis and cellular protection, and discuss the implications for disease treatment.

Keywords

Endoplasmic reticulum Mitochondria Unfolded protein response Neurodegenerative diseases Cancer Diabetes 

Abbreviations

6-OHDA

6-Hydroxydopamine

ALS

Amyotrophic lateral sclerosis

ASK1

Apoptosis signal-regulating kinase

ATF

Activating transcription factor

CHOP

C/EBP-homologous protein

CNS

Central nervous system

DOG

2-deoxy-D-glucose

DR5

Death receptor 5

eIF2α

Eukaryotic translation initiation factor 2α

ER

Endoplasmic reticulum

ERAD

ER-associated degradation

HPL-2

Heterochromatin protein like-2

IRE1

Inositol-requiring enzyme 1

JNK

Jun N-terminal kinase

Keap1

Kelch-like ECH-associated protein 1

MAM

Mitochondrial-associated ER membranes

PERK

Protein kinase RNA-like ER kinase

PI3K

Phosphoinositide 3-kinase

Rh1

Rhodopsin-1

RIDD

Regulated IRE1-dependent decay

ROS

Reactive oxygen species

S1P

Site 1 protease

UPR

Unfolded protein response

VCP

Valosin-containing protein

XBP1

X-box binding protein 1

Notes

Acknowledgments

This work was supported by grants from the Fondation ARC pour la Recherche sur le Cancer (SFI20121205951) and the Centre national de la recherche scientifique to BM, and from the Ligue Nationale Contre le Cancer (Comité du rhône) and Fondation ARC pour la Recherche sur le Cancer (PJA20131200334) to SM.

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Copyright information

© The International CCN Society 2014

Authors and Affiliations

  1. 1.Laboratory of Molecular Biology of the Cell, UMR5239 CNRS/Ecole Normale Supérieure de Lyon, UMS 3444 Biosciences Lyon GerlandUniversity of LyonLyonFrance
  2. 2.UMR CNRS 5286, INSERM 1052University of Lyon, Cancer Research Center of LyonLyonFrance

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