Mitochondrial membrane biogenesis requires the import of phospholipids; however, the molecular mechanisms underlying this process remain elusive. Recent work has implicated membrane contact sites between the mitochondria, endoplasmic reticulum (ER), and vacuole in phospholipid transport. Utilizing a genetic approach focused on these membrane contact site proteins, we have discovered a 'moonlighting' role of the membrane contact site and vesicular fusion protein, Vps39, in phosphatidylethanolamine (PE) transport to the mitochondria. We show that the deletion of Vps39 prevents ethanolamine-stimulated elevation of mitochondrial PE levels without affecting PE biosynthesis in the ER or its transport to other sub-cellular organelles. The loss of Vps39 did not alter the levels of other mitochondrial phospholipids that are biosynthesized ex situ, implying a PE-specific role of Vps39. The abundance of Vps39 and its recruitment to the mitochondria and the ER is dependent on PE levels in each of these organelles, directly implicating Vps39 in the PE transport process. Deletion of essential subunits of Vps39-containing complexes, vCLAMP and HOPS, did not abrogate ethanolamine-stimulated PE elevation in the mitochondria, suggesting an independent role of Vps39 in intracellular PE trafficking. Our work thus identifies Vps39 as a novel player in ethanolamine-stimulated PE transport to the mitochondria.

中文翻译：

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Vps39是线粒体磷脂酰乙醇胺中乙醇胺刺激的升高所必需的。

线粒体膜的生物发生需要磷脂的输入。然而，这个过程的分子机制仍然难以捉摸。最近的工作涉及磷脂运输中线粒体，内质网（ER）和液泡之间的膜接触部位。利用针对这些膜接触位点蛋白的遗传方法，我们发现了膜接触位点和囊泡融合蛋白Vps39在磷脂酰乙醇胺（PE）转运至线粒体中的“月光作用”。我们表明，删除Vps39可以防止乙醇胺刺激的线粒体PE水平升高，而不影响ER中的PE生物合成或将其运输到其他亚细胞器。Vps39的丧失并没有改变异位生物合成的其他线粒体磷脂的水平，暗示Vps39的PE特定作用。Vps39的丰度及其向线粒体和ER的募集取决于每个这些细胞器中的PE水平，直接将Vps39牵涉到PE的运输过程中。删除含有Vps39的复合物的必需亚基，vCLAMP和HOPS，并不能消除线粒体中乙醇胺刺激的PE升高，提示Vps39在细胞内PE交易中具有独立的作用。因此，我们的工作将Vps39鉴定为乙醇胺刺激的PE转运至线粒体的新途径。并没有消除线粒体中乙醇胺刺激的PE升高，提示Vps39在细胞内PE交易中具有独立的作用。因此，我们的工作将Vps39鉴定为乙醇胺刺激的PE转运至线粒体的新途径。并没有消除线粒体中乙醇胺刺激的PE升高，表明Vps39在细胞内PE交易中具有独立作用。因此，我们的工作将Vps39鉴定为乙醇胺刺激的PE转运至线粒体的新途径。