Institute for Clinical Diabetology, German Diabetes Center, c/o Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany.
German Center for Diabetes Research (DZD e.V.), München, Neuherberg, Germany.
J Cell Sci. 2018 Jun 11;131(11):jcs213876. doi: 10.1242/jcs.213876.
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 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.
脂滴 (LDs) 储存中性脂质，并整合到一个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，我们在 中进行了全局筛选，以鉴定在 LD 消耗过程中 LD 与其他细胞器之间功能耦合所必需的基因。我们表明，在生长恢复期间 LD 的利用与液泡动态平衡有关。ESCRT-、V-ATPase-和液泡蛋白分选突变体独立于脂噬作用负向影响 LD 的消耗。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，从 LD 近端部位到液泡的 DAG 通道被阻断。我们证明，LD 的利用需要通过 TORC1 及其下游效应物 Sit4p 来维持液泡信号。这些数据表明，通过 TORC1 介导的 DAG-PA 相互转化的调节，液泡状态与 LD 分解代谢偶联，并解释了细胞如何在整个细胞生长过程中协调细胞器动力学。
