The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy

Shiyan Liu, Mutian Chen, Yichang Wang, Yuqing Lei, Ting Huang, Yabin Zhang, Sin Man Lam, Huihui Li (), Shiqian Qi (), Jia Geng () and Kefeng Lu ()
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Shiyan Liu: Sichuan University
Mutian Chen: Sichuan University
Yichang Wang: Sichuan University
Yuqing Lei: West China Second University Hospital, Sichuan University
Ting Huang: Sichuan University
Yabin Zhang: Sichuan University
Sin Man Lam: Chinese Academy of Sciences
Huihui Li: West China Second University Hospital, Sichuan University
Shiqian Qi: Sichuan University
Jia Geng: Sichuan University
Kefeng Lu: Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-39482-6

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