Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase.
Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase.
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DOI：
10.1016/j.cmet.2011.07.013
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发表时间：
2011-10-05
期刊：
影响因子：
29
通讯作者：
Walther TC
中科院分区：
文献类型：
--
作者：
Krahmer N;Guo Y;Wilfling F;Hilger M;Lingrell S;Heger K;Newman HW;Schmidt-Supprian M;Vance DE;Mann M;Farese RV Jr;Walther TC
脂滴（LD）是中性脂质的细胞储存器，其大小和丰度根据细胞需要而变化。促进脂质储存的生理条件迅速和显着增加LD体积和表面。在这个过程中，对表面磷脂的需求是如何被感知和平衡的还不清楚。在这里，我们表明，磷脂酰胆碱（PC）作为一种表面活性剂，以防止LD聚结，否则会产生大的，抗脂解的LD和甘油三酯（TG）的积累。在LD扩增期间需要额外的PC来涂覆扩大的表面是由Kennedy途径提供的，该途径通过限速酶CTP：磷酸胆碱胞苷酰转移酶（CCT）可逆靶向生长的LD表面来激活。在果蝇和小鼠的细胞中，CCT对生长LD的需求、靶向和激活是相似的。我们的研究结果揭示了一种机制，以保持PC稳态在扩大LD单层通过有针对性地激活一个关键的PC合成酶。
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:phospho-cholin 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.
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影响因子：
64.8
作者：
Guo, Yi;Walther, Tobias C.;Farese, Robert V., Jr.
通讯作者：
Farese, Robert V., Jr.
DOI：
10.1165/rcmb.2005-0401oc
发表时间：
2006-09-01
影响因子：
6.4
作者：
McCoy, Diann M.;Fisher, Kurt;Mallampalli, Rama K.
通讯作者：
Mallampalli, Rama K.
影响因子：
56.9
作者：
Dobrosotskaya, IY;Seegmiller, AC;Rawson, RB
通讯作者：
Rawson, RB
DOI：
10.1016/j.bbalip.2004.04.008
发表时间：
2004-07-05
影响因子：
4.8
作者：
Helmink, BA;Friesen, JA
通讯作者：
Friesen, JA
影响因子：
4.8
作者：
Jacobs, RL;Devlin, C;Vance, DE
通讯作者：
Vance, DE