Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

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

Back
to Top