Protein Crowding Is a Determinant of Lipid Droplet Protein Composition.
Protein Crowding Is a Determinant of Lipid Droplet Protein Composition.
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DOI：
10.1016/j.devcel.2015.06.007
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发表时间：
2015-08-10
影响因子：
11.8
通讯作者：
Walther TC
中科院分区：
文献类型：
--
作者：
Kory N;Thiam AR;Farese RV Jr;Walther TC
脂滴（LD）是脂质储存细胞器，其生长或收缩取决于代谢能量的可用性。招募到ld的蛋白质介导许多代谢功能，包括磷脂酰胆碱和甘油三酯的合成。LD蛋白组成是如何根据脂质供给和需求进行调整的，目前尚不清楚。我们表明，与其他细胞器相比，ld具有有限的蛋白质结合能力。因此，大分子拥挤在决定LD蛋白组成中起主要作用。在脂肪分解过程中，当ld及其表面收缩时，一些（但不是全部）蛋白质发生位移。体外研究表明，大分子拥挤，而不是单层脂质组成的变化，导致蛋白质从LD表面脱落。正如拥挤模型所预测的那样，蛋白质会竞争与ld表面的结合。此外，LD结合亲和力决定了脂肪分解过程中蛋白质的定位。我们的研究结果确定蛋白质拥挤是决定LD蛋白质组成的重要原则。
Lipid droplets (LD) are lipid storage organelles that grow or shrink, depending on the availability of metabolic energy. Proteins recruited to LDs mediate many metabolic functions, including phosphatidylcholine and triglyceride synthesis. How the LD protein composition is tuned to the supply and demand for lipids remains unclear. We show that LDs, in contrast to other organelles, have limited capacity for protein binding. Consequently, macromolecular crowding plays a major role in determining LD protein composition. During lipolysis, when LDs and their surfaces shrink, some, but not all, proteins become displaced. In vitro studies show that macromolecular crowding, rather than changes in monolayer lipid composition, causes proteins to fall off the LD surface. As predicted by a crowding model, proteins compete for binding to the surfaces of LDs. Moreover, the LD binding affinity determines protein localization during lipolysis. Our findings identify protein crowding as an important principle in determining LD protein composition.