Vesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster
Vesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster
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DOI：
10.1038/s41467-020-16335-0
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发表时间：
2020-05-22
影响因子：
16.6
通讯作者：
Chen, Chun-Hong
中科院分区：
文献类型：
--
作者：
Chen, Po-Lin;Huang, Kai-Ting;Chen, Chun-Hong
线粒体老化导致线粒体功能障碍，与许多年龄相关疾病密切相关。衰老与线粒体增大和胞质蛋白质向线粒体的转运有关。调节线粒体形态和功能的潜在稳态机制及其在衰老过程中的分解仍不清楚。在这里，我们确定了一个线粒体蛋白质运输途径在果蝇涉及的果蝇相关蛋白Dosmit。多司米特诱导线粒体增大和线粒体内含有胞浆蛋白的双膜囊泡的形成。囊泡形成率随年龄增长而增加。通过跟踪Tom20定位观察到囊泡起源于线粒体外膜，并且该过程由与线粒体相关的Rab32蛋白介导。Dosmit表达水平与泛素化蛋白聚集的速率密切相关，而泛素化蛋白聚集本身与年龄相关疾病相关。Dosmit介导的线粒体蛋白运输途径为未来年龄相关线粒体疾病的治疗提供了一个有前途的靶点。线粒体动力学在衰老过程中发生变化，老年动物的线粒体更大，蛋白质输入也发生变化。在这里，作者表明，Dosmit蛋白介导的线粒体形态与Rab32诱导双膜囊泡，调节蛋白质运输到线粒体。
Mitochondrial aging, which results in mitochondrial dysfunction, is strongly linked to many age-related diseases. Aging is associated with mitochondrial enlargement and transport of cytosolic proteins into mitochondria. The underlying homeostatic mechanisms that regulate mitochondrial morphology and function, and their breakdown during aging, remain unclear. Here, we identify a mitochondrial protein trafficking pathway in Drosophila melanogaster involving the mitochondria-associated protein Dosmit. Dosmit induces mitochondrial enlargement and the formation of double-membraned vesicles containing cytosolic protein within mitochondria. The rate of vesicle formation increases with age. Vesicles originate from the outer mitochondrial membrane as observed by tracking Tom20 localization, and the process is mediated by the mitochondria-associated Rab32 protein. Dosmit expression level is closely linked to the rate of ubiquitinated protein aggregation, which are themselves associated with age-related diseases. The mitochondrial protein trafficking route mediated by Dosmit offers a promising target for future age-related mitochondrial disease therapies. Mitochondrial dynamics change during ageing, with larger mitochondria and altered protein import in older animals. Here the authors show that Dosmit protein mediates mitochondrial morphology with Rab32 by inducing double-membraned vesicles that regulate protein trafficking into mitochondria.