Lysosome lipid signalling from the periphery to neurons regulates longevity

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 reg...

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Autores principales: Savini, Marzia, Folick, Andrew, Lee, Yi-Tang, Jin, Feng, Cuevas, André, Tillman, Matthew C., Duffy, Jonathon D., Zhao, Qian, Neve, Isaiah A., Hu, Pei-Wen, Yu, Yong, Zhang, Qinghao, Ye, Youqiong, Mair, William B., Wang, Jin, Han, Leng, Ortlund, Eric A., Wang, Meng C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203275/
https://www.ncbi.nlm.nih.gov/pubmed/35681008
http://dx.doi.org/10.1038/s41556-022-00926-8
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author Savini, Marzia
Folick, Andrew
Lee, Yi-Tang
Jin, Feng
Cuevas, André
Tillman, Matthew C.
Duffy, Jonathon D.
Zhao, Qian
Neve, Isaiah A.
Hu, Pei-Wen
Yu, Yong
Zhang, Qinghao
Ye, Youqiong
Mair, William B.
Wang, Jin
Han, Leng
Ortlund, Eric A.
Wang, Meng C.
author_facet Savini, Marzia
Folick, Andrew
Lee, Yi-Tang
Jin, Feng
Cuevas, André
Tillman, Matthew C.
Duffy, Jonathon D.
Zhao, Qian
Neve, Isaiah A.
Hu, Pei-Wen
Yu, Yong
Zhang, Qinghao
Ye, Youqiong
Mair, William B.
Wang, Jin
Han, Leng
Ortlund, Eric A.
Wang, Meng C.
author_sort Savini, Marzia
collection PubMed
description 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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spelling pubmed-92032752022-06-18 Lysosome lipid signalling from the periphery to neurons regulates longevity Savini, Marzia Folick, Andrew Lee, Yi-Tang Jin, Feng Cuevas, André Tillman, Matthew C. Duffy, Jonathon D. Zhao, Qian Neve, Isaiah A. Hu, Pei-Wen Yu, Yong Zhang, Qinghao Ye, Youqiong Mair, William B. Wang, Jin Han, Leng Ortlund, Eric A. Wang, Meng C. Nat Cell Biol Article 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. Nature Publishing Group UK 2022-06-09 2022 /pmc/articles/PMC9203275/ /pubmed/35681008 http://dx.doi.org/10.1038/s41556-022-00926-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Savini, Marzia
Folick, Andrew
Lee, Yi-Tang
Jin, Feng
Cuevas, André
Tillman, Matthew C.
Duffy, Jonathon D.
Zhao, Qian
Neve, Isaiah A.
Hu, Pei-Wen
Yu, Yong
Zhang, Qinghao
Ye, Youqiong
Mair, William B.
Wang, Jin
Han, Leng
Ortlund, Eric A.
Wang, Meng C.
Lysosome lipid signalling from the periphery to neurons regulates longevity
title Lysosome lipid signalling from the periphery to neurons regulates longevity
title_full Lysosome lipid signalling from the periphery to neurons regulates longevity
title_fullStr Lysosome lipid signalling from the periphery to neurons regulates longevity
title_full_unstemmed Lysosome lipid signalling from the periphery to neurons regulates longevity
title_short Lysosome lipid signalling from the periphery to neurons regulates longevity
title_sort lysosome lipid signalling from the periphery to neurons regulates longevity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203275/
https://www.ncbi.nlm.nih.gov/pubmed/35681008
http://dx.doi.org/10.1038/s41556-022-00926-8
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