| First Author | Mocholi E | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112583 |
| PubMed ID | 37267106 | Mgi Jnum | J:337945 |
| Mgi Id | MGI:7508964 | Doi | 10.1016/j.celrep.2023.112583 |
| Citation | Mocholi E, et al. (2023) Pyruvate metabolism controls chromatin remodeling during CD4(+) T cell activation. Cell Rep 42(6):112583 |
| abstractText | Upon antigen-specific T cell receptor (TCR) engagement, human CD4(+) T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming. Here, we show that the generation of extramitochondrial pyruvate is an important step for acetyl-CoA production and subsequent H3K27ac-mediated remodeling of histone acetylation. Histone modification, transcriptomic, and carbon tracing analyses of pyruvate dehydrogenase (PDH)-deficient T cells show PDH-dependent acetyl-CoA generation as a rate-limiting step during T activation. Furthermore, T cell activation results in the nuclear translocation of PDH and its association with both the p300 acetyltransferase and histone H3K27ac. These data support the tight integration of metabolic and histone-modifying enzymes, allowing metabolic reprogramming to fuel CD4(+) T cell activation. Targeting this pathway may provide a therapeutic approach to specifically regulate antigen-driven T cell activation. |
