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- Title
The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy.
- Authors
Liu, Shiyan; Chen, Mutian; Wang, Yichang; Lei, Yuqing; Huang, Ting; Zhang, Yabin; Lam, Sin Man; Li, Huihui; Qi, Shiqian; Geng, Jia; Lu, Kefeng
- 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. Sphingolipids can function as lipid signaling molecules. Here, the authors find that the endoplasmic reticulum calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating calcium homeostasis in endoplasmic reticulum.
- Subjects
CALCIUM channels; RYANODINE receptors; HOMEOSTASIS; CALCIUM metabolism; AUTOPHAGY; METABOLISM; METABOLIC regulation; ENDOPLASMIC reticulum
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39482-6