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Publication Detail

Title: ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.

Authors: Zhao, Steven; Torres, AnnMarie; Henry, Ryan A; Trefely, Sophie; Wallace, Martina; Lee, Joyce V; Carrer, Alessandro; Sengupta, Arjun; Campbell, Sydney L; Kuo, Yin-Ming; Frey, Alexander J; Meurs, Noah; Viola, John M; Blair, Ian A; Weljie, Aalim M; Metallo, Christian M; Snyder, Nathaniel W; Andrews, Andrew J; Wellen, Kathryn E

Published In Cell Rep, (2016 10 18)

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.

PubMed ID: 27760311 Exiting the NIEHS site

MeSH Terms: ATP Citrate (pro-S)-Lyase/deficiency; ATP Citrate (pro-S)-Lyase/metabolism*; Acetate-CoA Ligase/metabolism; Acetates/metabolism*; Acetates/pharmacology; Acetyl Coenzyme A/metabolism; Acetylation; Adipocytes/drug effects; Adipocytes/metabolism; Animals; Cell Proliferation/drug effects; Cell Survival/drug effects; Fibroblasts/drug effects; Fibroblasts/metabolism; Gene Deletion; Glucose/metabolism*; Histones/metabolism; Lipid Metabolism/drug effects; Lipids/biosynthesis; Male; Mice; Up-Regulation/drug effects

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