2. Academic Validation
  3. An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis

An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis

  • Nat Commun. 2024 May 7;15(1):3793. doi: 10.1038/s41467-024-48189-1.
Stephen M Coscia 1 2 3,  Andrew S Moore 4,  Cameron P Thompson 1 2 5,  Christian F Tirrito 6 7,  E Michael Ostap 1 2,  Erika L F Holzbaur 8 9
Affiliations

Affiliations

  • 1 Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 2 Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 3 Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 4 Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, USA.
  • 5 Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 6 Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 7 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 8 Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. holzbaur@pennmedicine.upenn.edu.
  • 9 Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. holzbaur@pennmedicine.upenn.edu.
PMID: 38714822 DOI: 10.1038/s41467-024-48189-1
Abstract

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of Reactive Oxygen Species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.

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