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Title: From the unfolded protein response to metabolic diseases – lipids under the spotlight
Authors: Ho, Nurulain
Xu, Chengchao
Thibault, Guillaume
Keywords: Unfolded Protein Response
Endoplasmic Reticulum Stress
Issue Date: 2018
Source: Ho, N., Xu, C., & Thibault, G. (2018). From the unfolded protein response to metabolic diseases – lipids under the spotlight. Journal of Cell Science, 131, jcs199307-.
Series/Report no.: Journal of Cell Science
Abstract: The unfolded protein response (UPR) is classically viewed as a stress response pathway to maintain protein homeostasis at the endoplasmic reticulum (ER). However, it has recently emerged that the UPR can be directly activated by lipid perturbation, independently of misfolded proteins. Comprising primarily phospholipids, sphingolipids and sterols, individual membranes can contain hundreds of distinct lipids. Even with such complexity, lipid distribution in a cell is tightly regulated by mechanisms that remain incompletely understood. It is therefore unsurprising that lipid dysregulation can be a key factor in disease development. Recent advances in analysis of lipids and their regulators have revealed remarkable mechanisms and connections to other cellular pathways including the UPR. In this Review, we summarize the current understanding in UPR transducers functioning as lipid sensors and the interplay between lipid metabolism and ER homeostasis in the context of metabolic diseases. We attempt to provide a framework consisting of a few key principles to integrate the different lines of evidence and explain this rather complicated mechanism.
ISSN: 0021-9533
DOI: 10.1242/jcs.199307
Rights: © 2018 The Company of Biologists Ltd. This paper was published in Journal of Cell Science and is made available as an electronic reprint (preprint) with permission of The Company of Biologists Ltd. The published version is available at: []. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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