Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans

doi:10.1038/s41467-021-25398-6

	Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans
	Wang, Feng 1; Dai, Yuxi 1; Zhu, Xufeng2 ; Chen, Qilong 3; Zhu, Huanhu2 ; Zhou, Ben 3; Tang, Haiqing 1; Pang, Shanshan 1
	2021-08-20
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-25398-6
摘要	The membrane lipids change with ageing and function as regulatory molecules, but the underlying mechanisms are incompletely understood. Here, the authors identify C22 glucosylceramide as a regulator of the longevity transcription factor SKN-1, and show that C22 glucosylceramide regulates lifespan by controlling lysosome homeostasis and subsequent TOR activation. The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000687171500020
出版者	NATURE PORTFOLIO
原始文献类型	Article
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/131851
专题	生命科学与技术学院_硕士生生命科学与技术学院_PI研究组_朱焕乎组
通讯作者	Tang, Haiqing; Pang, Shanshan
作者单位	1.Chongqing Univ, Sch Life Sci, Chongqing, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 3.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Feng,Dai, Yuxi,Zhu, Xufeng,et al. Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Wang, Feng.,Dai, Yuxi.,Zhu, Xufeng.,Chen, Qilong.,Zhu, Huanhu.,...&Pang, Shanshan.(2021).Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans.NATURE COMMUNICATIONS,12(1).
MLA	Wang, Feng,et al."Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans".NATURE COMMUNICATIONS 12.1(2021).