title: De novo fatty acid synthesis at the mitotic exit is required to complete cellular division.
abstract: Although the regulation of the cell cycle has been extensively studied, much less is known about its coordination with the cellular metabolism. Using mass spectrometry we found that lysophospholipid levels decreased drastically from G 2/M to G 1 phase, while de novo phosphatidylcholine synthesis, the main phospholipid in mammalian cells, increased, suggesting that enhanced membrane production was concomitant to a decrease in its turnover. In addition, fatty acid synthesis and incorporation into membranes was increased upon cell division. The rate-limiting reaction for de novo fatty acid synthesis is catalyzed by acetyl-CoA carboxylase. As expected, its inhibiting phosphorylation decreased prior to cytokinesis initiation. Importantly, the inhibition of fatty acid synthesis arrested the cells at G 2/M despite the presence of abundant fatty acids in the media. Our results suggest that de novo lipogenesis is essential for cell cycle completion. This "lipogenic checkpoint" at G 2/M may be therapeutically exploited for hyperproliferative diseases such as cancer.
authors.affiliation: Department of Medical Oncology; Dana-Farber Cancer Institute; Harvard Medical School; Boston, MA USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Scaglia
authors.affiliation: Department of Biostatistics and Computational Biology; Dana-Farber Cancer Institute; Boston, MA USA; Department of Biostatistics; Harvard School of Public Health; Boston, MA USA.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Tyekucheva
authors.affiliation: Department of Medical Oncology; Dana-Farber Cancer Institute; Harvard Medical School; Boston, MA USA; Department of Pathology; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Zadra
authors.affiliation: Department of Medical Oncology; Dana-Farber Cancer Institute; Harvard Medical School; Boston, MA USA.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Photopoulos
authors.affiliation: Department of Medical Oncology; Dana-Farber Cancer Institute; Harvard Medical School; Boston, MA USA; Center for Molecular Oncologic Pathology; Dana-Farber Cancer Institute; Harvard Medical School; Boston, MA USA; Department of Pathology; Brigham and Women's Hospital; Harvard Medical School; Boston, MA USA; The Broad Institute; Cambridge, MA USA; Division of Cancer Studies; King's College London; London, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D005227:Fatty Acids / Q000096:biosynthesis*; D016193:G1 Phase; D059565:G2 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D053858:Metabolic Networks and Pathways; D008938:Mitosis
chemical_list: D005227:Fatty Acids; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase
keywords: AMPK; C75; cell cycle; cell cycle arrest; de novo lipogenesis; fatty acid; lysophospholipid; metabolome; phospholipid