Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins

Phospholipid homeostasis in biological membranes is essential to maintain functions of organelles such as the endoplasmic reticulum. Phospholipid perturbation has been associated to cellular stress responses. However, in most cases, the implication of membrane lipid changes to homeostatic cellular r...

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Main Authors: Ng, Benjamin S. H., Shyu Jr., Peter, Ho, Nurulain, Chaw, Ruijie, Seah, Yi Ling, Marvalim, Charlie, Thibault, Guillaume
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/89646
http://hdl.handle.net/10220/49317
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author Ng, Benjamin S. H.
Shyu Jr., Peter
Ho, Nurulain
Chaw, Ruijie
Seah, Yi Ling
Marvalim, Charlie
Thibault, Guillaume
author2 School of Biological Sciences
author_facet School of Biological Sciences
Ng, Benjamin S. H.
Shyu Jr., Peter
Ho, Nurulain
Chaw, Ruijie
Seah, Yi Ling
Marvalim, Charlie
Thibault, Guillaume
author_sort Ng, Benjamin S. H.
collection NTU
description Phospholipid homeostasis in biological membranes is essential to maintain functions of organelles such as the endoplasmic reticulum. Phospholipid perturbation has been associated to cellular stress responses. However, in most cases, the implication of membrane lipid changes to homeostatic cellular response has not been clearly defined. Previously, we reported that Saccharomyces cerevisiae adapts to lipid bilayer stress by upregulating several protein quality control pathways such as the endoplasmic reticulum-associated degradation (ERAD) pathway and the unfolded protein response (UPR). Surprisingly, we observed certain ER-resident transmembrane proteins, which form part of the UPR programme, to be destabilised under lipid bilayer stress. Among these, the protein translocon subunit Sbh1 was prematurely degraded by membrane stiffening at the ER. Moreover, our findings suggest that the Doa10 complex recognises free Sbh1 that becomes increasingly accessible during lipid bilayer stress, perhaps due to the change in ER membrane properties. Premature removal of key ER-resident transmembrane proteins might be an underlying cause of chronic ER stress as a result of lipid bilayer stress.
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spelling ntu-10356/896462023-02-28T16:58:34Z Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins Ng, Benjamin S. H. Shyu Jr., Peter Ho, Nurulain Chaw, Ruijie Seah, Yi Ling Marvalim, Charlie Thibault, Guillaume School of Biological Sciences Science::Biological sciences Endoplasmic Reticulum Phospholipids Phospholipid homeostasis in biological membranes is essential to maintain functions of organelles such as the endoplasmic reticulum. Phospholipid perturbation has been associated to cellular stress responses. However, in most cases, the implication of membrane lipid changes to homeostatic cellular response has not been clearly defined. Previously, we reported that Saccharomyces cerevisiae adapts to lipid bilayer stress by upregulating several protein quality control pathways such as the endoplasmic reticulum-associated degradation (ERAD) pathway and the unfolded protein response (UPR). Surprisingly, we observed certain ER-resident transmembrane proteins, which form part of the UPR programme, to be destabilised under lipid bilayer stress. Among these, the protein translocon subunit Sbh1 was prematurely degraded by membrane stiffening at the ER. Moreover, our findings suggest that the Doa10 complex recognises free Sbh1 that becomes increasingly accessible during lipid bilayer stress, perhaps due to the change in ER membrane properties. Premature removal of key ER-resident transmembrane proteins might be an underlying cause of chronic ER stress as a result of lipid bilayer stress. NRF (Natl Research Foundation, S’pore) Published version 2019-07-12T03:34:47Z 2019-12-06T17:30:13Z 2019-07-12T03:34:47Z 2019-12-06T17:30:13Z 2019 Journal Article Shyu Jr., P., Ng, B. S. H., Ho, N., Chaw, R., Seah, Y. L., Marvalim, C., & Thibault, G. (2019). Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins. Scientific Reports, 9(1), 8637-. doi:10.1038/s41598-019-45020-6 https://hdl.handle.net/10356/89646 http://hdl.handle.net/10220/49317 10.1038/s41598-019-45020-6 en Scientific Reports © 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 15 p. application/pdf
spellingShingle Science::Biological sciences
Endoplasmic Reticulum
Phospholipids
Ng, Benjamin S. H.
Shyu Jr., Peter
Ho, Nurulain
Chaw, Ruijie
Seah, Yi Ling
Marvalim, Charlie
Thibault, Guillaume
Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
title Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
title_full Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
title_fullStr Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
title_full_unstemmed Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
title_short Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins
title_sort membrane phospholipid alteration causes chronic er stress through early degradation of homeostatic er resident proteins
topic Science::Biological sciences
Endoplasmic Reticulum
Phospholipids
url https://hdl.handle.net/10356/89646
http://hdl.handle.net/10220/49317
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