title: Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase.
abstract: Lipid droplets (LDs) are cellular storage organelles for neutral lipids that vary in size and abundance according to cellular needs. Physiological conditions that promote lipid storage rapidly and markedly increase LD volume and surface. How the need for surface phospholipids is sensed and balanced during this process is unknown. Here, we show that phosphatidylcholine (PC) acts as a surfactant to prevent LD coalescence, which otherwise yields large, lipolysis-resistant LDs and triglyceride (TG) accumulation. The need for additional PC to coat the enlarging surface during LD expansion is provided by the Kennedy pathway, which is activated by reversible targeting of the rate-limiting enzyme, CTP:phosphocholine cytidylyltransferase (CCT), to growing LD surfaces. The requirement, targeting, and activation of CCT to growing LDs were similar in cells of Drosophila and mice. Our results reveal a mechanism to maintain PC homeostasis at the expanding LD monolayer through targeted activation of a key PC synthesis enzyme.
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Natalie
authors: N
authors: Krahmer
authors: Yi
authors: Y
authors: Guo
authors: Florian
authors: F
authors: Wilfling
authors: Maximiliane
authors: M
authors: Hilger
authors: Susanne
authors: S
authors: Lingrell
authors: Klaus
authors: K
authors: Heger
authors: Heather W
authors: HW
authors: Newman
authors: Marc
authors: M
authors: Schmidt-Supprian
authors: Dennis E
authors: DE
authors: Vance
authors: Matthias
authors: M
authors: Mann
authors: Robert V
authors: RV
authors: Farese
authors: Tobias C
authors: TC
authors: Walther
mesh_terms: D000818:Animals; D019916:Choline-Phosphate Cytidylyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D050356:Lipid Metabolism / Q000502:physiology*; D008066:Lipolysis; D051379:Mice; D019301:Oleic Acid / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000502:physiology*; D034622:RNA Interference; D014280:Triglycerides / Q000378:metabolism
chemical_list: D010713:Phosphatidylcholines; D014280:Triglycerides; D019301:Oleic Acid; D019916:Choline-Phosphate Cytidylyltransferase