Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:Phosphocholine cytidylyltransferase

Natalie Krahmer, Yi Guo, Florian Wilfling, Maximiliane Hilger, Susanne Lingrell, Klaus Heger, Heather W. Newman, Marc Schmidt-Supprian, Dennis E. Vance, Matthias Mann, Robert V. Farese, Tobias C. Walther

Research output: Contribution to journalArticle

249 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)504-515
Number of pages12
JournalCell Metabolism
Volume14
Issue number4
DOIs
StatePublished - Oct 5 2011

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Krahmer, N., Guo, Y., Wilfling, F., Hilger, M., Lingrell, S., Heger, K., Newman, H. W., Schmidt-Supprian, M., Vance, D. E., Mann, M., Farese, R. V., & Walther, T. C. (2011). Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:Phosphocholine cytidylyltransferase. Cell Metabolism, 14(4), 504-515. https://doi.org/10.1016/j.cmet.2011.07.013