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Am J Physiol Cell Physiol. 2015 Mar 15;308(6):C415-25. doi: 10.1152/ajpcell.00334.2014. Epub 2014 Dec 24.

The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease.

Author information

1
Centre National de la Recherche Scientifique, UMR8161, Institut de Biologie de Lille, Lille, France; Université Lille 1 Sciences et Techniques, Villeneuve d'Ascq, France; Université Lille 2 Droit et Santé, Lille, France; and Institut Pasteur de Lille, Lille, France olivier.pluquet@ibl.cnrs.fr.
2
Centre National de la Recherche Scientifique, UMR8161, Institut de Biologie de Lille, Lille, France; Université Lille 1 Sciences et Techniques, Villeneuve d'Ascq, France; Université Lille 2 Droit et Santé, Lille, France; and Institut Pasteur de Lille, Lille, France.

Abstract

The endoplasmic reticulum (ER) is a multifunctional organelle critical for the proper folding and assembly of secreted and transmembrane proteins. Perturbations of ER functions cause ER stress, which activates a coordinated system of transcriptional and translational controls called the unfolded protein response (UPR), to cope with accumulation of misfolded proteins and proteotoxicity. It results in ER homeostasis restoration or in cell death. Senescence is a complex cell phenotype induced by several stresses such as telomere attrition, DNA damage, oxidative stress, and activation of some oncogenes. It is mainly characterized by a cell enlargement, a permanent cell-cycle arrest, and the production of a secretome enriched in proinflammatory cytokines and components of the extracellular matrix. Senescent cells accumulate with age in tissues and are suspected to play a role in age-associated diseases. Since senescence is a stress response, the question arises of whether an ER stress could occur concomitantly with senescence and participate in the onset or maintenance of the senescent features. Here, we described the interconnections between the UPR signaling and the different aspects of the cellular senescence programs and discuss the implication of UPR modulations in this context.

KEYWORDS:

ATF6α; IRE1α; PERK; endoplasmic reticulum stress; oxidative stress; senescence; signaling; unfolded protein response

PMID:
25540175
DOI:
10.1152/ajpcell.00334.2014
[Indexed for MEDLINE]
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