Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration.
Roberto Bravo,Valentina Parra,Damián Gatica,Andrea E. Rodriguez,Natalia Torrealba,Felipe Paredes,Zhao V. Wang,Antonio Zorzano,Joseph A. Hill,Enrique Jaimovich,Andrew F. G. Quest,Sergio Lavandero,Sergio Lavandero +12 more
TLDR
In this article, the distinct functions of the endoplasmic reticulum (ER) and unfolded protein response (UPR) from a metabolic point of view are reviewed, highlighting their association with prevalent pathologies.Abstract:
The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of re-establishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies.read more
Citations
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Zinc ion plays a key role in ERp44-mediated protein quality control in the early secretory pathway
Yuta Amagai,Satoshi Watanabe,Manami Harayama,Momo Yamada,Sara Sannino,Roberto Sitia,Kenji Inaba +6 more
Abstract: Eukaryotic cells are able to discriminate between native and non‐native polypeptides, selectively transporting the former to their final destinations. Secretory proteins are scrutinized at the endoplasmic reticulum (ER)–Golgi interface. Recent findings reveal novel features of the underlying molecular mechanisms, with several chaperone networks cooperating in assisting the maturation of complex proteins and being selectively induced to match changing synthetic demands. ‘Public’ and ‘private’ chaperones, some of which enriched in specializes subregions, operate for most or selected substrates, respectively. Moreover, sequential checkpoints are distributed along the early secretory pathway, allowing efficiency and fidelity in protein secretion.
Journal ArticleDOI
Ca2+ homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling.
TL;DR: This work has shown that loss of nutrients/energy leads to the loss of cellular homeostasis and disruption of Ca(2+) signaling in both the reticular network and cytoplasmic compartments, and this leads to activation of ER stress coping responses, such as the unfolded protein response (UPR), and mobilization of pathways to regain ERHomeostasis.
Journal ArticleDOI
Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease
TL;DR: The role of endoplasmic reticulum (ER) stress response in the development of steatosis and progression to nonalcoholic steatohepatitis has been investigated in this paper.
Journal ArticleDOI
Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease.
TL;DR: The present review focuses on the role of ER stress and ROS in the pathogenesis of NAFLD and highlights the need for newer strategies with regards to ER Stress and oxidative stress.
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Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms
Luc Rochette,Charles Guenancia,Aurélie Gudjoncik,Olivier Hachet,Marianne Zeller,Yves Cottin,Catherine Vergely +6 more
TL;DR: Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors, but the use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction.
References
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Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus.
Caroline E. Shamu,Peter Walter +1 more
TL;DR: Molecular genetic and biochemical studies described here suggest that, as in the case of growth factor receptors of higher eukaryotic cells, Ire1p oligomerizes in response to the accumulation of unfolded proteins in the ER and is phosphorylated in trans by otherIre1p molecules as a result of oligomerization.
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The biology of vascular endothelial growth factor
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The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
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