{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kaymak I"],"funding":["NIAID NIH HHS","Fonds de Recherche du Québec—Santé","National Institutes of Health","Daymon Runyon Foundation","Chan Zuckerberg Initiative","Cancer Research Institute","National Institute of Allergy and Infectious Diseases","Fonds de Recherche du Québec-Santé","Cancer Research Society","Paul G. Allen Frontiers Group","Salk Pioneer Fund","National Cancer Institute","NCI NIH HHS","NIH HHS"],"pagination":["e20231820"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11329787"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(9)"],"pubmed_abstract":["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 metab"],"journal":["The Journal of experimental medicine"],"pubmed_title":["ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses."],"pmcid":["PMC11329787"],"funding_grant_id":["R01AI165722","R21 AI151986","R01 AI066232","R21AI153997","T32 CA251066","T32CA251066-01A1","R01 AI165722","PJT 192049","R21 AI153997","2495-23"],"pubmed_authors":["Kaymak I","Ma S","Watson MJ","Dahabieh MS","Williams KS","Fu Z","Vander Ark A","Kitchen-Goosen SM","Sheldon RD","Shen H","Mabvakure BM","Oswald BM","Kaech SM","Vos M","Johnson BK","Kingsbury GA","Sousa CM","DeCamp LM","Krawczyk CM","Ma EH","Roy DG","Roddy TP","Luda KM","Muhire B","Samborska B","Lau K","Jones RG","Fan ZP"],"additional_accession":[]},"is_claimable":false,"name":"ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses.","description":"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 metab","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-02T20:16:35.593Z","creation":"2025-04-07T07:53:20.514Z"},"accession":"S-EPMC11329787","cross_references":{"pubmed":["39150482"],"doi":["10.1084/jem.20231820"]}}