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 and Chun-Hong Chen ()
Additional contact information
Po-Lin Chen: National Health Research Institutes
Kai-Ting Huang: National Health Research Institutes
Chu-Ya Cheng: National Health Research Institutes
Jian-Chiuan Li: National Health Research Institutes
Hsiao-Yen Chan: National Health Research Institutes
Tzu-Yang Lin: Academia Sinica
Matthew P. Su: Nagoya University
Wei-Yuan Yang: Academia Sinica
Henry C. Chang: Purdue University
Horng-Dar Wang: National Tsing Hua University
Chun-Hong Chen: National Health Research Institutes

Nature Communications, 2020, vol. 11, issue 1, 1-19

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16335-0

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