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Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria

Author

Listed:
  • Huan Yang

    (UCLA David Geffen School of Medicine)

  • Caroline Sibilla

    (National Institute of Neurological Disorders and Stroke
    University College London School of Pharmacy
    AstraZeneca PLC, Cambridge Biomedical Campus)

  • Raymond Liu

    (California Institute of Technology
    Department of Microbiology and Immunology, UCSF)

  • Jina Yun

    (UCLA David Geffen School of Medicine
    Genentech, Inc.)

  • Bruce A. Hay

    (California Institute of Technology)

  • Craig Blackstone

    (National Institute of Neurological Disorders and Stroke
    Harvard Medical School)

  • David C. Chan

    (California Institute of Technology)

  • Robert J. Harvey

    (University of the Sunshine Coast
    Sunshine Coast Health Institute)

  • Ming Guo

    (UCLA David Geffen School of Medicine
    UCLA David Geffen School of Medicine
    California NanoSystems Institute at UCLA)

Abstract

Mitochondrial fission is critically important for controlling mitochondrial morphology, function, quality and transport. Drp1 is the master regulator driving mitochondrial fission, but exactly how Drp1 is regulated remains unclear. Here, we identified Drosophila Clueless and its mammalian orthologue CLUH as key regulators of Drp1. As with loss of drp1, depletion of clueless or CLUH results in mitochondrial elongation, while as with drp1 overexpression, clueless or CLUH overexpression leads to mitochondrial fragmentation. Importantly, drp1 overexpression rescues adult lethality, tissue disintegration and mitochondrial defects of clueless null mutants in Drosophila. Mechanistically, Clueless and CLUH promote recruitment of Drp1 to mitochondria from the cytosol. This involves CLUH binding to mRNAs encoding Drp1 receptors MiD49 and Mff, and regulation of their translation. Our findings identify a crucial role of Clueless and CLUH in controlling mitochondrial fission through regulation of Drp1.

Suggested Citation

  • Huan Yang & Caroline Sibilla & Raymond Liu & Jina Yun & Bruce A. Hay & Craig Blackstone & David C. Chan & Robert J. Harvey & Ming Guo, 2022. "Clueless/CLUH regulates mitochondrial fission by promoting recruitment of Drp1 to mitochondria," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29071-4
    DOI: 10.1038/s41467-022-29071-4
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