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SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination

Lipid droplets (LDs) are involved in various biological events in cells along with their primary role as a storage center for neutral lipids. Excessive accumulation of LDs is highly correlated with various diseases, including metabolic diseases. Therefore, a basic understanding of the molecular mech...

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Autores principales: Jung, Jinjoo, Park, Jongbeom, Kim, Mingi, Ha, Jaeyoung, Cho, Hana, Park, Seung Bum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030462/
https://www.ncbi.nlm.nih.gov/pubmed/36944894
http://dx.doi.org/10.1038/s42003-023-04682-9
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author Jung, Jinjoo
Park, Jongbeom
Kim, Mingi
Ha, Jaeyoung
Cho, Hana
Park, Seung Bum
author_facet Jung, Jinjoo
Park, Jongbeom
Kim, Mingi
Ha, Jaeyoung
Cho, Hana
Park, Seung Bum
author_sort Jung, Jinjoo
collection PubMed
description Lipid droplets (LDs) are involved in various biological events in cells along with their primary role as a storage center for neutral lipids. Excessive accumulation of LDs is highly correlated with various diseases, including metabolic diseases. Therefore, a basic understanding of the molecular mechanism of LD degradation would be beneficial in both academic and industrial research. Lipophagy, a selective autophagy mechanism/LD degradation process, has gained increased attention in the research community. Herein, we sought to elucidate a novel lipophagy mechanism by utilizing the LD-degrading small molecule, SB2301, which activates ubiquitin-mediated lipophagy. Using a label-free target identification method, we revealed that ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) is a potential target protein of SB2301. We also demonstrated that although SB2301 does not modulate PCYT2 function, it induces the cellular translocation of PCYT2 to the LD surface and spatially increases the phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio of the LD membrane, causing LD coalescence, leading to the activation of lipophagy process to maintain energy homeostasis.
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spelling pubmed-100304622023-03-23 SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination Jung, Jinjoo Park, Jongbeom Kim, Mingi Ha, Jaeyoung Cho, Hana Park, Seung Bum Commun Biol Article Lipid droplets (LDs) are involved in various biological events in cells along with their primary role as a storage center for neutral lipids. Excessive accumulation of LDs is highly correlated with various diseases, including metabolic diseases. Therefore, a basic understanding of the molecular mechanism of LD degradation would be beneficial in both academic and industrial research. Lipophagy, a selective autophagy mechanism/LD degradation process, has gained increased attention in the research community. Herein, we sought to elucidate a novel lipophagy mechanism by utilizing the LD-degrading small molecule, SB2301, which activates ubiquitin-mediated lipophagy. Using a label-free target identification method, we revealed that ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) is a potential target protein of SB2301. We also demonstrated that although SB2301 does not modulate PCYT2 function, it induces the cellular translocation of PCYT2 to the LD surface and spatially increases the phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio of the LD membrane, causing LD coalescence, leading to the activation of lipophagy process to maintain energy homeostasis. Nature Publishing Group UK 2023-03-21 /pmc/articles/PMC10030462/ /pubmed/36944894 http://dx.doi.org/10.1038/s42003-023-04682-9 Text en © The Author(s) 2023 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
Jung, Jinjoo
Park, Jongbeom
Kim, Mingi
Ha, Jaeyoung
Cho, Hana
Park, Seung Bum
SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
title SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
title_full SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
title_fullStr SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
title_full_unstemmed SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
title_short SB2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
title_sort sb2301-mediated perturbation of membrane composition in lipid droplets induces lipophagy and lipid droplets ubiquitination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030462/
https://www.ncbi.nlm.nih.gov/pubmed/36944894
http://dx.doi.org/10.1038/s42003-023-04682-9
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