| First Author | Zhao S | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 4 | Pages | 1037-1052 |
| PubMed ID | 27760311 | Mgi Jnum | J:240494 |
| Mgi Id | MGI:5883672 | Doi | 10.1016/j.celrep.2016.09.069 |
| Citation | Zhao S, et al. (2016) ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch. Cell Rep 17(4):1037-1052 |
| abstractText | 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. |
