ATP citrate lyase is an important component of cell growth and transformation

Oncogene. 2005 Sep 15;24(41):6314-22. doi: 10.1038/sj.onc.1208773.


Cell proliferation requires a constant supply of lipids and lipid precursors to fuel membrane biogenesis and protein modification. Cytokine stimulation of hematopoietic cells directly stimulates glucose utilization in excess of bioenergetic demand, resulting in a shift from oxidative to glycolytic metabolism. A potential benefit of this form of metabolism is the channeling of glucose into biosynthetic pathways. Here we report that glucose supports de novo lipid synthesis in growing hematopoietic cells in a manner regulated by cytokine availability and the PI 3 K/Akt signaling pathway. The net conversion of glucose to lipid is dependent on the ability of cells to produce cytosolic acetyl CoA from mitochondria-derived citrate through the action of ATP citrate lyase (ACL). Stable knockdown of ACL leads to a significant impairment of glucose-dependent lipid synthesis and an elevation of mitochondrial membrane potential. Cells with ACL knockdown display decreased cytokine-stimulated cell proliferation. In contrast, these cells resist cell death induced by either cytokine or glucose withdrawal. However, ACL knockdown significantly impairs Akt-mediated tumorigenesis in vivo. These data suggest that enzymes involved in the conversion of glucose to lipid may be targets for the treatment of pathologic cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Citrate (pro-S)-Lyase / physiology*
  • Amino Acid Sequence
  • Cell Division / physiology*
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Flow Cytometry
  • Molecular Sequence Data


  • ATP Citrate (pro-S)-Lyase