Phosphatidylcholine Synthesis for Lipid Droplet Expansion Is Mediated by Localized Activation of CTP:Phosphocholine Cytidylyltransferase

被引：392

作者：

Krahmer, Natalie ^{[1
,3
]}

Guo, Yi ^{[1
]}

Wilfling, Florian

Hilger, Maximiliane ^{[3
]}

Lingrell, Susanne ^{[4
,5
]}

Heger, Klaus ^{[3
]}

Newman, Heather W. ^{[2
]}

Schmidt-Supprian, Marc ^{[3
]}

Vance, Dennis E. ^{[4
,5
]}

Mann, Matthias

Farese, Robert V., Jr. ^{[2
,6
,7
]}

Walther, Tobias C. ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA

[2] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA

[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[4] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada

[5] Univ Alberta, Grp Mol & Cell Biol Lipids, Edmonton, AB T6G 2H7, Canada

[6] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[7] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA

来源：

CELL METABOLISM | 2011年 / 14卷 / 04期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; DROSOPHILA-MELANOGASTER; ENDOPLASMIC-RETICULUM; RAT-LIVER; BIOSYNTHESIS; TRANSLOCATION; CHOLINE; BINDING; CELLS; STIMULATION;

D O I：

10.1016/j.cmet.2011.07.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：504 / 515

页数：12

共 46 条

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