Lactate is a bridge linking glycolysis and autophagy through lactylation

Lactate is a glycolysis product that is produced from pyruvate by LDH (lactate dehydrogenase) and plays an important role in physiological and pathological processes. However, whether lactate regulates autophagy is still unknown. We recently reported that LDHA is phosphorylated at serine 196 by ULK1...

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Autores principales: Sun, Weixia, Jia, Mengshu, Feng, Yingyan, Cheng, Xiawei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Autophagic Punctum
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621282/
https://www.ncbi.nlm.nih.gov/pubmed/37565742
http://dx.doi.org/10.1080/15548627.2023.2246356
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author Sun, Weixia
Jia, Mengshu
Feng, Yingyan
Cheng, Xiawei
author_facet Sun, Weixia
Jia, Mengshu
Feng, Yingyan
Cheng, Xiawei
author_sort Sun, Weixia
collection PubMed
description Lactate is a glycolysis product that is produced from pyruvate by LDH (lactate dehydrogenase) and plays an important role in physiological and pathological processes. However, whether lactate regulates autophagy is still unknown. We recently reported that LDHA is phosphorylated at serine 196 by ULK1 (unc-51 like kinase 1) under nutrient-deprivation conditions, promoting lactate production. Then, lactate mediates PIK3C3/VPS34 lactylation at lysine 356 and lysine 781 via acyltransferase KAT5/TIP60. PIK3C3/VPS34 lactylation enhances the association of PIK3C3/VPS34 with BECN1 (beclin 1, autophagy related), ATG14 and UVRAG, increases PIK3C3/VPS34 lipid kinase activity, promotes macroautophagy/autophagy and facilitates the endolysosomal degradation pathway. PIK3C3/VPS34 hyperlactylation induces autophagy and plays an essential role in skeletal muscle homeostasis and cancer progression. Overall, this study describes an autophagy regulation mechanism and the integration of two highly conserved life processes: glycolysis and autophagy.
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spelling pubmed-106212822023-11-03 Lactate is a bridge linking glycolysis and autophagy through lactylation Sun, Weixia Jia, Mengshu Feng, Yingyan Cheng, Xiawei Autophagy Autophagic Punctum Lactate is a glycolysis product that is produced from pyruvate by LDH (lactate dehydrogenase) and plays an important role in physiological and pathological processes. However, whether lactate regulates autophagy is still unknown. We recently reported that LDHA is phosphorylated at serine 196 by ULK1 (unc-51 like kinase 1) under nutrient-deprivation conditions, promoting lactate production. Then, lactate mediates PIK3C3/VPS34 lactylation at lysine 356 and lysine 781 via acyltransferase KAT5/TIP60. PIK3C3/VPS34 lactylation enhances the association of PIK3C3/VPS34 with BECN1 (beclin 1, autophagy related), ATG14 and UVRAG, increases PIK3C3/VPS34 lipid kinase activity, promotes macroautophagy/autophagy and facilitates the endolysosomal degradation pathway. PIK3C3/VPS34 hyperlactylation induces autophagy and plays an essential role in skeletal muscle homeostasis and cancer progression. Overall, this study describes an autophagy regulation mechanism and the integration of two highly conserved life processes: glycolysis and autophagy. Taylor & Francis 2023-08-18 /pmc/articles/PMC10621282/ /pubmed/37565742 http://dx.doi.org/10.1080/15548627.2023.2246356 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Autophagic Punctum
Sun, Weixia
Jia, Mengshu
Feng, Yingyan
Cheng, Xiawei
Lactate is a bridge linking glycolysis and autophagy through lactylation
title Lactate is a bridge linking glycolysis and autophagy through lactylation
title_full Lactate is a bridge linking glycolysis and autophagy through lactylation
title_fullStr Lactate is a bridge linking glycolysis and autophagy through lactylation
title_full_unstemmed Lactate is a bridge linking glycolysis and autophagy through lactylation
title_short Lactate is a bridge linking glycolysis and autophagy through lactylation
title_sort lactate is a bridge linking glycolysis and autophagy through lactylation
topic Autophagic Punctum
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621282/
https://www.ncbi.nlm.nih.gov/pubmed/37565742
http://dx.doi.org/10.1080/15548627.2023.2246356
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AT jiamengshu lactateisabridgelinkingglycolysisandautophagythroughlactylation
AT fengyingyan lactateisabridgelinkingglycolysisandautophagythroughlactylation
AT chengxiawei lactateisabridgelinkingglycolysisandautophagythroughlactylation

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