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

Author

Listed:
  • Po-Lin Chen

    (National Health Research Institutes
    National Health Research Institutes
    National Taiwan University)

  • Kai-Ting Huang

    (National Health Research Institutes
    National Tsing Hua University)

  • Chu-Ya Cheng

    (National Health Research Institutes)

  • Jian-Chiuan Li

    (National Health Research Institutes
    National Health Research Institutes)

  • Hsiao-Yen Chan

    (National Health Research Institutes
    National Tsing Hua University)

  • 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
    National Health Research Institutes
    National Taiwan University
    National Health Research Institutes)

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.

Suggested Citation

  • 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 & Chun-Hong Chen, 2020. "Vesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16335-0
    DOI: 10.1038/s41467-020-16335-0
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    Cited by:

    1. Su Jin Ham & Heesuk Yoo & Daihn Woo & Da Hyun Lee & Kyu-Sang Park & Jongkyeong Chung, 2023. "PINK1 and Parkin regulate IP3R-mediated ER calcium release," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Edward T. Schmid & Joseph M. Schinaman & Naomi Liu-Abramowicz & Kylie S. Williams & David W. Walker, 2024. "Accumulation of F-actin drives brain aging and limits healthspan in Drosophila," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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