Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in cellular metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. During LD biogenesis and growth, this monolayer of lipids expands by acquiring phospholipids from the endoplasmic reticulum (ER) through nonvesicular mechanisms. Here, in a mini-screen, we find that ORP5, an integral membrane protein of the ER, can localize to ER–LD contact sites upon oleate loading. ORP5 interacts with LDs through its ligand-binding domain, and ORP5 deficiency enhances neutral lipid synthesis and increases the size of LDs. Importantly, there is significantly more phosphatidylinositol-4-phosphate (PI(4)P) and less phosphatidylserine (PS) on LDs in ORP5-deficient cells than in normal cells. The increased presence of PI(4)P on LDs in ORP5-deficient cells requires phosphatidylinositol 4-kinase 2-α. Our results thus demonstrate the existence of PI(4)P on LDs and suggest that LD-associated PI(4)P may be primarily used by ORP5 to deliver PS to LDs.

中文翻译：

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ORP5 定位于 ER-脂滴接触并调节脂滴上 PI(4)P 的水平

脂滴（LD）是进化上保守的细胞器，在细胞代谢中发挥重要作用。每个 LD 都被单层磷脂包围，与双层膜不同。在 LD 生物发生和生长过程中，这种单层脂质通过非囊泡机制从内质网 (ER) 获取磷脂而扩张。在这里，在迷你筛选中，我们发现 ORP5（ER 的一种整合膜蛋白）可以在油酸负载后定位到 ER-LD 接触位点。ORP5 通过其配体结合域与 LD 相互作用，ORP5 缺陷会增强中性脂质合成并增加 LD 的大小。重要的是，ORP5 缺陷细胞中的 LD 上的磷脂酰肌醇 4-磷酸 (PI(4)P) 显着高于正常细胞，而磷脂酰丝氨酸 (PS) 显着低于正常细胞。ORP5 缺陷细胞中 LD 上 PI(4)P 的增加需要磷脂酰肌醇 4-激酶 2-α。因此，我们的结果证明了 LD 上存在 PI(4)P，并表明 LD 相关的 PI(4)P 可能主要被 ORP5 用于向 LD 传递 PS。