Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis.
We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth.
Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK miguel.sanchez@cnic.es.
Miguel
M
Sanchez-Alvarez
Lipidomics Facility, Babraham Institute, Cambridge CB22 3AT, UK.
Qifeng
Q
Zhang
Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Fabian
F
Finger
Lipidomics Facility, Babraham Institute, Cambridge CB22 3AT, UK.
Michael J O
MJ
Wakelam
Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK cbakal@icr.ac.uk.
Chris
C
Bakal
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013936:Thymidine / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D029721:Drosophila Proteins; D007328:Insulin; D046912:Multiprotein Complexes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; D051779:Sterol Regulatory Element Binding Proteins; D016159:Tumor Suppressor Protein p53; C483858:phosphatidylethanolamine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D013936:Thymidine
Drosophila; cell cycle progression; endoplasmic reticulum homeostasis; lipidomics; phospholipid metabolism; sterol response element binding proteins