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

Natalie Krahmer, Yi D 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

227 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Choline-Phosphate Cytidylyltransferase
Phosphatidylcholines
Lipids
Lipid Droplets
Lipolysis
Enzymes
Surface-Active Agents
Organelles
Drosophila
Phospholipids
Triglycerides
Homeostasis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP : Phosphocholine cytidylyltransferase. / Krahmer, Natalie; Guo, Yi D; Wilfling, Florian; Hilger, Maximiliane; Lingrell, Susanne; Heger, Klaus; Newman, Heather W.; Schmidt-Supprian, Marc; Vance, Dennis E.; Mann, Matthias; Farese, Robert V.; Walther, Tobias C.

In: Cell Metabolism, Vol. 14, No. 4, 05.10.2011, p. 504-515.

Research output: Contribution to journalArticle

Krahmer, N, Guo, YD, Wilfling, F, Hilger, M, Lingrell, S, Heger, K, Newman, HW, Schmidt-Supprian, M, Vance, DE, Mann, M, Farese, RV & Walther, TC 2011, 'Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP: Phosphocholine cytidylyltransferase', Cell Metabolism, vol. 14, no. 4, pp. 504-515. https://doi.org/10.1016/j.cmet.2011.07.013
Krahmer, Natalie ; Guo, Yi D ; Wilfling, Florian ; Hilger, Maximiliane ; Lingrell, Susanne ; Heger, Klaus ; Newman, Heather W. ; Schmidt-Supprian, Marc ; Vance, Dennis E. ; Mann, Matthias ; Farese, Robert V. ; Walther, Tobias C. / Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP : Phosphocholine cytidylyltransferase. In: Cell Metabolism. 2011 ; Vol. 14, No. 4. pp. 504-515.
@article{9ed6a7f395ae4b6bb105dedf12ae5f1a,
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.",
author = "Natalie Krahmer and Guo, {Yi D} and Florian Wilfling and Maximiliane Hilger and Susanne Lingrell and Klaus Heger and Newman, {Heather W.} and Marc Schmidt-Supprian and Vance, {Dennis E.} and Matthias Mann and Farese, {Robert V.} and Walther, {Tobias C.}",
year = "2011",
month = "10",
day = "5",
doi = "10.1016/j.cmet.2011.07.013",
language = "English (US)",
volume = "14",
pages = "504--515",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP

T2 - Phosphocholine cytidylyltransferase

AU - Krahmer, Natalie

AU - Guo, Yi D

AU - Wilfling, Florian

AU - Hilger, Maximiliane

AU - Lingrell, Susanne

AU - Heger, Klaus

AU - Newman, Heather W.

AU - Schmidt-Supprian, Marc

AU - Vance, Dennis E.

AU - Mann, Matthias

AU - Farese, Robert V.

AU - Walther, Tobias C.

PY - 2011/10/5

Y1 - 2011/10/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80053927108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053927108&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2011.07.013

DO - 10.1016/j.cmet.2011.07.013

M3 - Article

C2 - 21982710

AN - SCOPUS:80053927108

VL - 14

SP - 504

EP - 515

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -