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Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts

Author

Listed:
  • Kangqiang Qiu

    (University of Cincinnati College of Medicine)

  • Weiwei Zou

    (Cincinnati Children’s Hospital Medical Center)

  • Hongbao Fang

    (University of Cincinnati College of Medicine)

  • Mingang Hao

    (University of Cincinnati College of Medicine)

  • Kritika Mehta

    (University of Illinois at Urbana-Champaign)

  • Zhiqi Tian

    (University of Cincinnati College of Medicine)

  • Jun-Lin Guan

    (University of Cincinnati College of Medicine)

  • Kai Zhang

    (University of Illinois at Urbana-Champaign)

  • Taosheng Huang

    (Cincinnati Children’s Hospital Medical Center
    University at Buffalo)

  • Jiajie Diao

    (University of Cincinnati College of Medicine)

Abstract

Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria–lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46−/− cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.

Suggested Citation

  • Kangqiang Qiu & Weiwei Zou & Hongbao Fang & Mingang Hao & Kritika Mehta & Zhiqi Tian & Jun-Lin Guan & Kai Zhang & Taosheng Huang & Jiajie Diao, 2022. "Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31970-5
    DOI: 10.1038/s41467-022-31970-5
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    References listed on IDEAS

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    1. Yvette C. Wong & Daniel Ysselstein & Dimitri Krainc, 2018. "Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis," Nature, Nature, vol. 554(7692), pages 382-386, February.
    2. Nina A. Bonekamp & Bradley Peter & Hauke S. Hillen & Andrea Felser & Tim Bergbrede & Axel Choidas & Moritz Horn & Anke Unger & Raffaella Lucrezia & Ilian Atanassov & Xinping Li & Uwe Koch & Sascha Men, 2020. "Small-molecule inhibitors of human mitochondrial DNA transcription," Nature, Nature, vol. 588(7839), pages 712-716, December.
    3. Jonathan R. Friedman & Jodi Nunnari, 2014. "Mitochondrial form and function," Nature, Nature, vol. 505(7483), pages 335-343, January.
    4. Maxime Boutry & Peter K. Kim, 2021. "ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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