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Vesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster
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Vesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster

Po-Lin Chen, Kai-Ting Huang, Chu-Ya Cheng, Jian-Chiuan Li, Hsiao-Yen Chan, Tzu-Yang Lin, Matthew P. Su, Wei-Yuan Yang, Henry C. Chang, Horng-Dar Wang, …
Nature Communications, 卷.11(1), 2592
12/2020
PMID: 32444642

摘要

Chemistry (all) Biochemistry Genetics and Molecular Biology (all) Multidisciplinary Physics and Astronomy (all)
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.

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https://doi.org/10.1038/s41467-020-16335-0檢視
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