An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER
An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER
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DOI：
10.1016/j.celrep.2013.11.046
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发表时间：
2014-01-01
期刊：
影响因子：
8.8
通讯作者：
Rapoport, Tom A.
中科院分区：
文献类型：
--
作者：
Markgraf, Daniel F.;Klemm, Robin W.;Rapoport, Tom A.
真核细胞将中性脂质如三酰甘油（TAG）储存在脂滴（LD）中。在这里，我们已经解决了LD是如何在功能上连接到内质网（ER）。我们证明，在S。在酿酒酵母中，LD生长由LD定位的酶维持。当LD在早期稳定期生长时，二酰基甘油酰基转移酶Dga1p从ER移动到LD，并负责从二酰基甘油（DAG）合成所有TAG。在早期指数阶段的LD击穿期间，ER膜蛋白（Ice2p）促进TAG用于膜脂质合成。Ice2p具有对LD具有亲和力的胞质结构域，并且是ER中有效利用LD衍生的DAG所需的。Ice2p打破了TAG降解和合成之间的LD无效循环，促进Dga1p快速重新定位到ER。我们的研究结果表明，Ice2p在功能上将LD与ER联系起来，并解释了细胞如何将中性脂质代谢从储存转换为消耗。
Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.