| First Author | Kaymak I | Year | 2024 |
| Journal | J Exp Med | Volume | 221 |
| Issue | 9 | PubMed ID | 39150482 |
| Mgi Jnum | J:360713 | Mgi Id | MGI:7787193 |
| Doi | 10.1084/jem.20231820 | Citation | Kaymak I, et al. (2024) ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses. J Exp Med 221(9) |
| abstractText | Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that CD8 T cell responses to infection depend on acetyl-CoA derived from citrate via the enzyme ATP citrate lyase (ACLY). However, ablation of ACLY triggers an alternative, acetate-dependent pathway for acetyl-CoA production mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and chromatin accessibility at effector gene loci. When ACLY is functional, ACSS2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, loss of ACLY renders CD8 T cells dependent on acetate (via ACSS2) to maintain acetyl-CoA production and effector function. Together, ACLY and ACSS2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function. |
