| First Author | Jing X | Year | 2023 |
| Journal | Mol Biol Cell | Volume | 34 |
| Issue | 7 | Pages | br10 |
| PubMed ID | 37133968 | Mgi Jnum | J:352740 |
| Mgi Id | MGI:7519987 | Doi | 10.1091/mbc.E23-02-0070 |
| Citation | Jing X, et al. (2023) Acetate regulates GAPDH acetylation and T helper 1 cell differentiation. Mol Biol Cell 34(7):br10 |
| abstractText | 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. |
