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Acetate regulates GAPDH acetylation and T helper 1 cell differentiation
The short-chain fatty acid metabolite acetyl-coenzyme A (acetyl-CoA) has emerged as a major signal transducer that can broadly affect cell fate and function, at least partly by influencing acetylation of key proteins. The mechanism by which acetyl-CoA regulates CD4(+) T-cell fate determination remai...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295475/ https://www.ncbi.nlm.nih.gov/pubmed/37133968 http://dx.doi.org/10.1091/mbc.E23-02-0070 |
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author | Jing, Xizhong Lyu, Junfang Xiong, Jianhua |
author_facet | Jing, Xizhong Lyu, Junfang Xiong, Jianhua |
author_sort | Jing, Xizhong |
collection | PubMed |
description | The short-chain fatty acid metabolite acetyl-coenzyme A (acetyl-CoA) has emerged as a major signal transducer that can broadly affect cell fate and function, at least partly by influencing acetylation of key proteins. The mechanism by which acetyl-CoA regulates CD4(+) T-cell fate determination remains poorly understood. Herein, we report that acetate modulates glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acetylation and CD4(+) T helper 1 (Th1) cell differentiation by altering acetyl-CoA levels. Our transcriptome profiling shows that acetate is a robust positive regulator of CD4(+) T-cell gene expression typical of glycolysis. We further show that acetate potentiates GAPDH activity, aerobic glycolysis, and Th1 polarization through regulation of GAPDH acetylation levels. This acetate-dependent GAPDH acetylation occurs in a dose- and time-dependent manner, while decreasing acetyl-CoA levels by fatty acid oxidation inhibition results in a decline in acetyl-GAPDH levels. Thus, acetate functions as a potent metabolic regulator in CD4(+) T-cells by promoting GAPDH acetylation and Th1 cell fate decision. |
format | Online Article Text |
id | pubmed-10295475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-102954752023-08-16 Acetate regulates GAPDH acetylation and T helper 1 cell differentiation Jing, Xizhong Lyu, Junfang Xiong, Jianhua Mol Biol Cell Brief Reports The short-chain fatty acid metabolite acetyl-coenzyme A (acetyl-CoA) has emerged as a major signal transducer that can broadly affect cell fate and function, at least partly by influencing acetylation of key proteins. The mechanism by which acetyl-CoA regulates CD4(+) T-cell fate determination remains poorly understood. Herein, we report that acetate modulates glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acetylation and CD4(+) T helper 1 (Th1) cell differentiation by altering acetyl-CoA levels. Our transcriptome profiling shows that acetate is a robust positive regulator of CD4(+) T-cell gene expression typical of glycolysis. We further show that acetate potentiates GAPDH activity, aerobic glycolysis, and Th1 polarization through regulation of GAPDH acetylation levels. This acetate-dependent GAPDH acetylation occurs in a dose- and time-dependent manner, while decreasing acetyl-CoA levels by fatty acid oxidation inhibition results in a decline in acetyl-GAPDH levels. Thus, acetate functions as a potent metabolic regulator in CD4(+) T-cells by promoting GAPDH acetylation and Th1 cell fate decision. The American Society for Cell Biology 2023-06-01 /pmc/articles/PMC10295475/ /pubmed/37133968 http://dx.doi.org/10.1091/mbc.E23-02-0070 Text en © 2023 Jing et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License. |
spellingShingle | Brief Reports Jing, Xizhong Lyu, Junfang Xiong, Jianhua Acetate regulates GAPDH acetylation and T helper 1 cell differentiation |
title | Acetate regulates GAPDH acetylation and T helper 1 cell differentiation |
title_full | Acetate regulates GAPDH acetylation and T helper 1 cell differentiation |
title_fullStr | Acetate regulates GAPDH acetylation and T helper 1 cell differentiation |
title_full_unstemmed | Acetate regulates GAPDH acetylation and T helper 1 cell differentiation |
title_short | Acetate regulates GAPDH acetylation and T helper 1 cell differentiation |
title_sort | acetate regulates gapdh acetylation and t helper 1 cell differentiation |
topic | Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295475/ https://www.ncbi.nlm.nih.gov/pubmed/37133968 http://dx.doi.org/10.1091/mbc.E23-02-0070 |
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