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

Feng Wang, Yuxi Dai, Xufeng Zhu, Qilong Chen, Huanhu Zhu, Ben Zhou, Haiqing Tang () and Shanshan Pang ()
Additional contact information
Feng Wang: Chongqing University
Yuxi Dai: Chongqing University
Xufeng Zhu: ShanghaiTech University
Qilong Chen: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Huanhu Zhu: ShanghaiTech University
Ben Zhou: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Haiqing Tang: Chongqing University
Shanshan Pang: Chongqing University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25398-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25398-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25398-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().