{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":47,"searchCount":0},"additional":{"submitter":["Zhao S"],"funding":["NICHD NIH HHS","NIEHS NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["1037-1052"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5175409"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(4)"],"pubmed_abstract":["Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL) and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency."],"journal":["Cell reports"],"pubmed_title":["ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch."],"pmcid":["PMC5175409"],"funding_grant_id":["P30 CA016520","P30 ES013508","T32 CA115299","K22 ES026235","R21 HD087866","K12 GM081259","R01 CA188652","R01 GM102503","P30 CA006927","R01 CA174761","F31 CA189744"],"pubmed_authors":["Campbell SL","Wallace M","Carrer A","Wellen KE","Trefely S","Andrews AJ","Blair IA","Viola JM","Henry RA","Frey AJ","Metallo CM","Lee JV","Sengupta A","Kuo YM","Meurs N","Zhao S","Weljie AM","Snyder NW","Torres A"],"view_count":["47"],"additional_accession":[]},"is_claimable":false,"name":"ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.","description":"Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis (DNL) and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Together, these data indicate that engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Oct","modification":"2020-10-31T09:11:06Z","creation":"2019-03-27T02:32:12Z"},"accession":"S-EPMC5175409","cross_references":{"pubmed":["27760311"],"doi":["10.1016/j.celrep.2016.09.069"]}}