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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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    1. Tohru Kitada & Shuichi Asakawa & Nobutaka Hattori & Hiroto Matsumine & Yasuhiro Yamamura & Shinsei Minoshima & Masayuki Yokochi & Yoshikuni Mizuno & Nobuyoshi Shimizu, 1998. "Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism," Nature, Nature, vol. 392(6676), pages 605-608, April.
    2. Raghav Kalia & Ray Yu-Ruei Wang & Ali Yusuf & Paul V. Thomas & David A. Agard & Janet M. Shaw & Adam Frost, 2018. "Structural basis of mitochondrial receptor binding and constriction by DRP1," Nature, Nature, vol. 558(7710), pages 401-405, June.
    3. Ira E. Clark & Mark W. Dodson & Changan Jiang & Joseph H. Cao & Jun R. Huh & Jae Hong Seol & Soon Ji Yoo & Bruce A. Hay & Ming Guo, 2006. "Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin," Nature, Nature, vol. 441(7097), pages 1162-1166, June.
    4. Nikolay P. Kandul & Ting Zhang & Bruce A. Hay & Ming Guo, 2016. "Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
    5. Michael Lazarou & Danielle A. Sliter & Lesley A. Kane & Shireen A. Sarraf & Chunxin Wang & Jonathon L. Burman & Dionisia P. Sideris & Adam I. Fogel & Richard J. Youle, 2015. "The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy," Nature, Nature, vol. 524(7565), pages 309-314, August.
    6. Michael T. D. Cooper & Sarah J. Bray, 1999. "Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye," Nature, Nature, vol. 397(6719), pages 526-530, February.
    7. David I. Strutt & Ursula Weber & Marek Mlodzik, 1997. "The role of RhoA in tissue polarity and Frizzled signalling," Nature, Nature, vol. 387(6630), pages 292-295, May.
    8. Jeehye Park & Sung Bae Lee & Sungkyu Lee & Yongsung Kim & Saera Song & Sunhong Kim & Eunkyung Bae & Jaeseob Kim & Minho Shong & Jin-Man Kim & Jongkyeong Chung, 2006. "Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin," Nature, Nature, vol. 441(7097), pages 1157-1161, June.
    9. Fumika Koyano & Kei Okatsu & Hidetaka Kosako & Yasushi Tamura & Etsu Go & Mayumi Kimura & Yoko Kimura & Hikaru Tsuchiya & Hidehito Yoshihara & Takatsugu Hirokawa & Toshiya Endo & Edward A. Fon & Jean-, 2014. "Ubiquitin is phosphorylated by PINK1 to activate parkin," Nature, Nature, vol. 510(7503), pages 162-166, June.
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