Cholesterol Overload: Contact Sites to the Rescue!
Cholesterol Overload: Contact Sites to the Rescue!
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DOI：
10.1177/2515256419893507
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Eden, Emily R
中科院分区：
文献类型：
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作者：
Enrich, Carlos;Rentero, Carles;Eden, Emily R
低密度脂蛋白源性胆固醇向内质网（ER）的转运对于胆固醇的稳态是必不可少的，但这种转运的机制在很大程度上仍然是难以捉摸的。最近的两份报告揭示了这一过程，揭示了尼曼匹克C1型蛋白（NPC 1）在晚期内体（LE）/溶酶体（Lys）和ER之间形成膜接触位点（MCS）的作用。这两项研究都确定了缺乏功能性NPC 1的细胞中MCS的损失，其中胆固醇在晚期内吞细胞器中积累。值得注意的是，这两项研究采用不同的方法，得出了惊人的观察结果，即LE/Lys-ER MCS的扩增可以挽救NPC 1突变或缺陷细胞中的胆固醇积累表型。在这两种情况下，胆固醇都被转运到ER，证明了ER-LE/Lys接触位点在低密度脂蛋白衍生的胆固醇直接转运到ER中的重要性。
Delivery of low-density lipoprotein-derived cholesterol to the endoplasmic reticulum (ER) is essential for cholesterol homeostasis, yet the mechanism of this transport has largely remained elusive. Two recent reports shed some light on this process, uncovering a role for Niemann Pick type-C1 protein (NPC1) in the formation of membrane contact sites (MCS) between late endosomes (LE)/lysosomes (Lys) and the ER. Both studies identified a loss of MCS in cells lacking functional NPC1, where cholesterol accumulates in late endocytic organelles. Remarkably, and taking different approaches, both studies have made a striking observation that expansion of LE/Lys-ER MCS can rescue the cholesterol accumulation phenotype in NPC1 mutant or deficient cells. In both cases, the cholesterol was shown to be transported to the ER, demonstrating the importance of ER-LE/Lys contact sites in the direct transport of low-density lipoprotein-derived cholesterol to the ER.