Vps39 Interacts with Tom40 to Establish One of Two Functionally Distinct Vacuole-Mitochondria Contact Sites
Vps39 Interacts with Tom40 to Establish One of Two Functionally Distinct Vacuole-Mitochondria Contact Sites
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DOI：
10.1016/j.devcel.2018.05.011
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发表时间：
2018-06-04
影响因子：
11.8
通讯作者：
Ungermann, Christian
中科院分区：
文献类型：
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作者：
Montoro, Ayelen Gonzalez;Auffarth, Kathrin;Ungermann, Christian
广泛的亚细胞膜接触点网络在细胞器的生物发生和通信中起着核心作用，但所涉及的机制的确切贡献在很大程度上仍然是个谜。酵母空泡与线粒体形成膜接触位点，称为空泡和线粒体斑（vCLAMP）。vCLAMPs的形成涉及HOPS系链复合物的液泡Rab GT3 Ypt 7和Ypt 7相互作用的Vps 39亚基。在这里，我们发现外膜（TOM）亚基的一般前蛋白移位酶Tom 40作为线粒体上Vps 39的直接结合伴侣。我们确定Vps 39突变体缺陷的TOM结合，但功能的HOPS。不能形成vCLAMP的细胞在应激条件下显示生长减少，并且在饥饿时存活受损。出乎意料的是，我们的突变体分析揭示了两个功能独立的液泡-线粒体MCS的存在：一个由Ypt 7-Vps 39-Tom 40系链形成，第二个由Vps 13-Mcp 1形成，这与ERMES形成的ER-线粒体接触是多余的。
The extensive subcellular network of membrane contact sites plays central roles in organelle biogenesis and communication, yet the precise contributions of the involved machineries remain largely enigmatic. The yeast vacuole forms a membrane contact site with mitochondria, called vacuolar and mitochondrial patch (vCLAMP). Formation of vCLAMPs involves the vacuolar Rab GTPase Ypt7 and the Ypt7-interacting Vps39 subunit of the HOPS tethering complex. Here, we uncover the general preprotein translocase of the outer membrane (TOM) subunit Tom40 as the direct binding partner of Vps39 on mitochondria. We identify Vps39 mutants defective in TOM binding, but functional for HOPS. Cells that cannot form vCLAMPs show reduced growth under stress conditions and impaired survival upon starvation. Unexpectedly, our mutant analysis revealed the existence of two functionally independent vacuole-mitochondria MCSs: one formed by the Ypt7-Vps39-Tom40 tether and a second one by Vps13-Mcp1, which is redundant with ER-mitochondrial contacts formed by ERMES.