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The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy

Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we find that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calci...

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Autores principales: Liu, Shiyan, Chen, Mutian, Wang, Yichang, Lei, Yuqing, Huang, Ting, Zhang, Yabin, Lam, Sin Man, Li, Huihui, Qi, Shiqian, Geng, Jia, Lu, Kefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287731/
https://www.ncbi.nlm.nih.gov/pubmed/37349354
http://dx.doi.org/10.1038/s41467-023-39482-6
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author Liu, Shiyan
Chen, Mutian
Wang, Yichang
Lei, Yuqing
Huang, Ting
Zhang, Yabin
Lam, Sin Man
Li, Huihui
Qi, Shiqian
Geng, Jia
Lu, Kefeng
author_facet Liu, Shiyan
Chen, Mutian
Wang, Yichang
Lei, Yuqing
Huang, Ting
Zhang, Yabin
Lam, Sin Man
Li, Huihui
Qi, Shiqian
Geng, Jia
Lu, Kefeng
author_sort Liu, Shiyan
collection PubMed
description Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we find that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. Csg2 functions as a calcium release channel and maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase Aur1. Under starvation conditions, deletion of Csg2 causes increases in calcium levels in the ER and then disturbs Aur1 stability, leading to accumulation of the bioactive sphingolipid phytosphingosine, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the channel Csg2 translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy.
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spelling pubmed-102877312023-06-24 The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy Liu, Shiyan Chen, Mutian Wang, Yichang Lei, Yuqing Huang, Ting Zhang, Yabin Lam, Sin Man Li, Huihui Qi, Shiqian Geng, Jia Lu, Kefeng Nat Commun Article Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we find that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. Csg2 functions as a calcium release channel and maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase Aur1. Under starvation conditions, deletion of Csg2 causes increases in calcium levels in the ER and then disturbs Aur1 stability, leading to accumulation of the bioactive sphingolipid phytosphingosine, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the channel Csg2 translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy. Nature Publishing Group UK 2023-06-22 /pmc/articles/PMC10287731/ /pubmed/37349354 http://dx.doi.org/10.1038/s41467-023-39482-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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. The 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Shiyan
Chen, Mutian
Wang, Yichang
Lei, Yuqing
Huang, Ting
Zhang, Yabin
Lam, Sin Man
Li, Huihui
Qi, Shiqian
Geng, Jia
Lu, Kefeng
The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
title The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
title_full The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
title_fullStr The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
title_full_unstemmed The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
title_short The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy
title_sort er calcium channel csg2 integrates sphingolipid metabolism with autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287731/
https://www.ncbi.nlm.nih.gov/pubmed/37349354
http://dx.doi.org/10.1038/s41467-023-39482-6
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