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Mitochondria- and ER-associated actin are required for mitochondrial fusion

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  • Priya Gatti

    (Université du Québec à Trois-Rivières
    Université du Québec à Montréal
    Réseau Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ))

  • Cara Schiavon

    (University of California)

  • Julien Cicero

    (University of California)

  • Uri Manor

    (University of California)

  • Marc Germain

    (Université du Québec à Trois-Rivières
    Université du Québec à Montréal
    Réseau Intersectoriel de Recherche en Santé de l’Université du Québec (RISUQ))

Abstract

Mitochondria are crucial for cellular metabolism and signalling. Mitochondrial activity is modulated by mitochondrial fission and fusion, which are required to properly balance metabolic functions, transfer material between mitochondria, and remove defective mitochondria. Mitochondrial fission occurs at mitochondria-endoplasmic reticulum (ER) contact sites, and requires the formation of actin filaments that drive mitochondrial constriction and the recruitment of the fission protein DRP1. The role of actin in mitochondrial fusion remains entirely unexplored. Here we show that preventing actin polymerisation on either mitochondria or the ER disrupts both fission and fusion. We show that fusion but not fission is dependent on Arp2/3, whereas both fission and fusion require INF2 formin-dependent actin polymerization. We also show that mitochondria-associated actin marks fusion sites prior to the fusion protein MFN2. Together, our work introduces a method for perturbing organelle-associated actin and demonstrates a previously unknown role for actin in mitochondrial fusion.

Suggested Citation

  • Priya Gatti & Cara Schiavon & Julien Cicero & Uri Manor & Marc Germain, 2025. "Mitochondria- and ER-associated actin are required for mitochondrial fusion," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55758-x
    DOI: 10.1038/s41467-024-55758-x
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    References listed on IDEAS

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    1. Andrew S. Moore & Yvette C. Wong & Cory L. Simpson & Erika L. F. Holzbaur, 2016. "Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission–fusion balance within mitochondrial networks," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    2. Andrew S. Moore & Stephen M. Coscia & Cory L. Simpson & Fabian E. Ortega & Eric C. Wait & John M. Heddleston & Jeffrey J. Nirschl & Christopher J. Obara & Pedro Guedes-Dias & C. Alexander Boecker & Te, 2021. "Actin cables and comet tails organize mitochondrial networks in mitosis," Nature, Nature, vol. 591(7851), pages 659-664, March.
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