Lipid droplet consumption is functionally coupled to vacuole homeostasis independent of lipophagy
Lipid droplet consumption is functionally coupled to vacuole homeostasis independent of lipophagy
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DOI：
10.1242/jcs.213876
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发表时间：
2018-06-01
影响因子：
4
通讯作者：
Markgraf, Daniel F.
中科院分区：
文献类型：
--
作者：
Ouahoud, Sarah;Fiet, Mitchell D.;Markgraf, Daniel F.
脂滴（LD）储存中性脂质，并整合到依赖于与各种细胞器功能耦合的细胞代谢网络中。介导有效耦合的因素和调节它们的机制仍然未知。在这里，我们进行了一个全球性的屏幕在S。酿酒酵母，以确定所需的基因的功能耦合LD和其他细胞器在LD消费。我们表明，LD利用生长恢复过程中耦合到液泡的稳态。ESCRT-，V-ATPase-和液泡蛋白分选突变体负面影响LD消费，独立的脂肪吞噬。ESCRT功能的丧失导致LD衍生的二酰基甘油（DAG）的积累，阻止其转化为磷脂酸（PA）和膜脂质。此外，DAG从LD近端位点到液泡的通道被阻断。我们证明，利用LD需要完整的空泡信号通过TORC 1及其下游效应Sit 4p。这些数据表明，空泡状态耦合到LD catalysts通过TORC 1介导的调节DAG-PA的相互转换，并解释细胞如何协调整个细胞生长的细胞器动力学。
Lipid droplets (LDs) store neutral lipids and are integrated into a cellular metabolic network that relies on functional coupling with various organelles. Factors mediating efficient coupling and mechanisms regulating them remain unknown. Here, we conducted a global screen in S. cerevisiae to identify genes required for the functional coupling of LDs and other organelles during LD consumption. We show that LD utilization during growth resumption is coupled to vacuole homeostasis. ESCRT-, V-ATPase- and vacuole protein sorting-mutants negatively affect LD consumption, independent of lipophagy. Loss of ESCRT function leads to the accumulation of LD-derived diacylglycerol (DAG), preventing its conversion into phosphatidic acid (PA) and membrane lipids. In addition, channeling of DAG from LD-proximal sites to the vacuole is blocked. We demonstrate that utilization of LDs requires intact vacuolar signaling via TORC1 and its downstream effector Sit4p. These data suggest that vacuolar status is coupled to LD catabolism via TORC1-mediated regulation of DAG-PA interconversion and explain how cells coordinate organelle dynamics throughout cell growth.