细胞生物学
生物
脂质代谢
溶酶体
长寿
细胞信号
信号转导
生物化学
酶
遗传学
作者
Marzia Savini,Andrew Folick,Yi-Tang Lee,Feng Jin,André Cuevas,Matthew C. Tillman,Jonathon Duffy,Qian Zhao,Isaiah A.A. Neve,Pei-Wen Hu,Yong Yu,Qinghao Zhang,Youqiong Ye,William B. Mair,Jin Wang,Leng Han,Eric A. Ortlund,Meng C. Wang
标识
DOI:10.1038/s41556-022-00926-8
摘要
Abstract Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in ageing-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate ageing remains unclear. Here we report a fat-to-neuron lipid signalling pathway induced by lysosomal metabolism and its longevity-promoting role in Caenorhabditis elegans . We discovered that induced lysosomal lipolysis in peripheral fat storage tissue upregulates the neuropeptide signalling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a specific polyunsaturated fatty acid, dihomo-γ-linolenic acid, and LBP-3 lipid chaperone protein transported from the fat storage tissue to neurons. LBP-3 binds to dihomo-γ-linolenic acid, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signalling hub to coordinate metabolism and ageing, and lysosomal signalling mediated inter-tissue communication in promoting longevity.
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