The UPRER: Sensor and Coordinator of Organismal Homeostasis

Life is stressful. Organisms are repeatedly exposed to stressors that disrupt protein homeostasis (proteostasis), resulting in protein misfolding and aggregation. To sense and respond to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein...

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Bibliographic Details
Published in:Molecular cell 2017-06, Vol.66 (6), p.761-771
Main Authors: Frakes, Ashley E., Dillin, Andrew
Format: Article
Language:English
Subjects:
aging
amyotrophic lateral sclerosis
chronic inflammation
endoplasmic reticulum
ER stress
metabolic disease
NF-kappaB
protein aggregation
unfolded protein response
XBP1
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Summary:Life is stressful. Organisms are repeatedly exposed to stressors that disrupt protein homeostasis (proteostasis), resulting in protein misfolding and aggregation. To sense and respond to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPRER). However, UPRER function is impaired with age, which, we propose, creates a permissive environment for protein aggregation, unresolved ER stress, and chronic inflammation. Understanding age-related changes to the UPRER will provide new avenues for therapeutic intervention in metabolic disease, neurodegeneration, and aging. To sense and respond to proteotoxic perturbations, cells induce stress responses such as the unfolded protein response of the endoplasmic reticulum (UPRER). Here, Frakes and Dillin review the mechanisms by which UPRER coordinates organismal homeostasis and how UPRER impairment lies at the nexus of aging, chronic inflammation, and metabolic and neurodegenerative disease.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2017.05.031