Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes.
Date Issued
2019-01
Date Acceptance
2018-07-18
Citation
FEBS Journal, 2019, 286 (2), pp.241-278
ISSN
0014-2956
Publisher
Wiley
Start Page
241
End Page
278
Journal / Book Title
FEBS Journal
Volume
286
Issue
2
Copyright Statement
© 2018 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Commission of the European Communities
Identifier
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14608
Grant Number
675448
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
endoplasmic reticulum
proteostasis
signalling pathway
stress
UNFOLDED PROTEIN RESPONSE
TO-MESENCHYMAL TRANSITION
PLASMA-CELL DIFFERENTIATION
PANCREATIC BETA-CELLS
BOX-BINDING PROTEIN-1
MESSENGER-RNA DECAY
ER-STRESS
TRANSCRIPTION FACTOR
QUALITY-CONTROL
GLUCOSE-HOMEOSTASIS
endoplasmic reticulum
proteostasis
signalling pathway
stress
Animals
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Homeostasis
Humans
Signal Transduction
Unfolded Protein Response
Endoplasmic Reticulum
Animals
Humans
Signal Transduction
Homeostasis
Unfolded Protein Response
Endoplasmic Reticulum Stress
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
0304 Medicinal and Biomolecular Chemistry
Biochemistry & Molecular Biology
Publication Status
Published
Date Publish Online
2018-07-20