VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis.
VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis.
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DOI：
10.1083/jcb.201608128
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Kim PK
中科院分区：
文献类型：
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作者：
Hua R;Cheng D;Coyaud É;Freeman S;Di Pietro E;Wang Y;Vissa A;Yip CM;Fairn GD;Braverman N;Brumell JH;Trimble WS;Raught B;Kim PK
过氧化物酶体和ER交换脂质以进行各种代谢和合成代谢反应。在这项研究中，Hua等人表明，ER驻留VAP与过氧化物酶体蛋白ACBD 5之间的相互作用将过氧化物酶体束缚在ER上。这条系链是两个细胞器之间交换脂质（包括胆固醇）所必需的。在哺乳动物细胞中，内质网（ER）和过氧化物酶体之间的脂质交换对于脂质的合成和分解、胆固醇的运输以及过氧化物酶体的生物合成是必需的。然而，这两种细胞器之间的脂质交换方式尚不清楚。在这项研究中，我们报告说，ER居民的VAMP相关蛋白A和B（VAPA和VAP B）与过氧化物酶体膜蛋白酰基辅酶A结合域5（ACBD 5）相互作用，这种相互作用是必需的系在一起的两个细胞器，从而促进它们之间的脂质交换。ACBD 5或VAP表达的耗竭导致过氧化物酶体迁移率增加，表明VAP-ACBD 5复合物充当主要ER-过氧化物酶体系链。我们还表明，过氧化物酶体的ER的拴系是必要的过氧化物酶体的生长，合成的缩醛磷脂，和细胞胆固醇水平的维持。总的来说，我们的数据突出了VAP-ACBD 5介导的ER和过氧化物酶体之间的接触对细胞器维持和脂质稳态的重要性。
Peroxisomes and the ER exchange lipids for various metabolic and anabolic reactions. In this study, Hua et al. show that the interaction between the ER-resident VAPs with the peroxisomal protein ACBD5 tethers peroxisomes to the ER. This tether is required for the exchange of lipids, including cholesterol, between the two organelles. Lipid exchange between the endoplasmic reticulum (ER) and peroxisomes is necessary for the synthesis and catabolism of lipids, the trafficking of cholesterol, and peroxisome biogenesis in mammalian cells. However, how lipids are exchanged between these two organelles is not understood. In this study, we report that the ER-resident VAMP-associated proteins A and B (VAPA and VAPB) interact with the peroxisomal membrane protein acyl-CoA binding domain containing 5 (ACBD5) and that this interaction is required to tether the two organelles together, thereby facilitating the lipid exchange between them. Depletion of either ACBD5 or VAP expression results in increased peroxisome mobility, suggesting that VAP–ACBD5 complex acts as the primary ER–peroxisome tether. We also demonstrate that tethering of peroxisomes to the ER is necessary for peroxisome growth, the synthesis of plasmalogen phospholipids, and the maintenance of cellular cholesterol levels. Collectively, our data highlight the importance of VAP–ACBD5–mediated contact between the ER and peroxisomes for organelle maintenance and lipid homeostasis.