Cellular Metabolism Regulates Contact Sites between Vacuoles and Mitochondria
Cellular Metabolism Regulates Contact Sites between Vacuoles and Mitochondria
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DOI：
10.1016/j.devcel.2014.06.006
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发表时间：
2014-07-01
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：
Hoenscher, Canna;Mari, Muriel;Ungermann, Christian
新出现的证据表明，不同细胞器之间的接触点形成协调细胞生理学的中心枢纽。虽然最近的工作强调了内质网在细胞器间串扰中的关键作用，但其他细胞器的合作行为在很大程度上尚未探索。在这里，我们确定了一个名为vCLAMP（空泡和线粒体补丁），整合线粒体与溶酶体样空泡，从而内吞途径的接触网站。vCLAMPs依赖于液泡HOPS拴系复合物亚基Vps 39/Vam 6和Rab GTp 3 Ypt 7，它们也参与液泡处的膜融合。有趣的是，vCLAMPs位于ER-线粒体相遇结构（ERMES）复合物附近，vCLAMPs的增加可以挽救ERMES突变体的生长缺陷。重要的是，vCLAMPs的持久性受Vps 39磷酸化的调节，并且在呼吸生长期间强烈降低。该细胞器接触位点的鉴定揭示了内吞途径和线粒体之间的物理和代谢互连。
Emerging evidence suggests that contact sites between different organelles form central hubs in the coordination of cellular physiology. Although recent work has emphasized the crucial role of the endoplasmic reticulum in interorganellar crosstalk, the cooperative behavior of other organelles is largely unexplored. Here, we identify a contact site named vCLAMP (vacuole and mitochondria patch) that integrates mitochondria with the lysosome-like vacuole and thus the endocytic pathway. vCLAMPs depend on the vacuolar HOPS tethering complex subunit Vps39/Vam6 and the Rab GTPase Ypt7, which also participate in membrane fusion at the vacuole. Intriguingly, vCLAMPs are located proximal to the ER-mitochondria encounter structure (ERMES) complexes, and an increase in vCLAMPs can rescue the growth defect of ERMES mutants. Importantly, the persistence of vCLAMPs is regulated by phosphorylation of Vps39 and is strongly reduced during respiratory growth. The identification of this organelle contact site reveals a physical and metabolic interconnection between the endocytic pathway and mitochondria.