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DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass

Author

Listed:
  • Giulia Favaro

    (Venetian Institute of Molecular Medicine
    University of Padova)

  • Vanina Romanello

    (Venetian Institute of Molecular Medicine
    University of Padova
    University of Padova)

  • Tatiana Varanita

    (University of Padova)

  • Maria Andrea Desbats

    (University of Padova
    IRP Città della Speranza Corso Stati Uniti 4)

  • Valeria Morbidoni

    (University of Padova
    IRP Città della Speranza Corso Stati Uniti 4)

  • Caterina Tezze

    (Venetian Institute of Molecular Medicine
    University of Padova)

  • Mattia Albiero

    (Venetian Institute of Molecular Medicine
    University of Padova)

  • Marta Canato

    (University of Padova)

  • Gaia Gherardi

    (University of Padova)

  • Diego Stefani

    (University of Padova)

  • Cristina Mammucari

    (University of Padova)

  • Bert Blaauw

    (Venetian Institute of Molecular Medicine
    University of Padova
    University of Padova)

  • Simona Boncompagni

    (via Luigi Polacchi, University G. d’ Annunzio)

  • Feliciano Protasi

    (via Luigi Polacchi, University G. d’ Annunzio)

  • Carlo Reggiani

    (University of Padova
    Science and Research Center of Koper)

  • Luca Scorrano

    (Venetian Institute of Molecular Medicine
    University of Padova)

  • Leonardo Salviati

    (University of Padova
    IRP Città della Speranza Corso Stati Uniti 4)

  • Marco Sandri

    (Venetian Institute of Molecular Medicine
    University of Padova
    University of Padova
    McGill University)

Abstract

Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca2+ uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca2+ handling.

Suggested Citation

  • Giulia Favaro & Vanina Romanello & Tatiana Varanita & Maria Andrea Desbats & Valeria Morbidoni & Caterina Tezze & Mattia Albiero & Marta Canato & Gaia Gherardi & Diego Stefani & Cristina Mammucari & B, 2019. "DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10226-9
    DOI: 10.1038/s41467-019-10226-9
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    Cited by:

    1. Andrea Irazoki & Isabel Gordaliza-Alaguero & Emma Frank & Nikolaos Nikiforos Giakoumakis & Jordi Seco & Manuel Palacín & Anna Gumà & Lykke Sylow & David Sebastián & Antonio Zorzano, 2023. "Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Prasanna Katti & Peter T. Ajayi & Angel Aponte & Christopher K. E. Bleck & Brian Glancy, 2022. "Identification of evolutionarily conserved regulators of muscle mitochondrial network organization," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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