Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission–fusion balance within mitochondrial networks

Andrew S. Moore, Yvette C. Wong, Cory L. Simpson and Erika L. F. Holzbaur ()
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Andrew S. Moore: Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
Yvette C. Wong: Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
Cory L. Simpson: Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
Erika L. F. Holzbaur: Perelman School of Medicine, University of Pennsylvania, 638A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Mitochondria form interconnected networks that dynamically remodel in response to cellular needs. Using live-cell imaging, we investigate the role of the actin cytoskeleton in regulating mitochondrial fission and fusion. We identify cycling of actin filaments onto and off of subsets of cellular mitochondria. The association of actin filaments with mitochondrial subpopulations is transient; actin quickly disassembles, then reassembles around a distinct subpopulation, efficiently cycling through all cellular mitochondria within 14 min. The focal assembly of actin induces local, Drp1-dependent fragmentation of the mitochondrial network. On actin disassembly, fragmented mitochondria undergo rapid fusion, leading to regional recovery of the tubular mitochondrial network. Cycling requires dynamic actin polymerization and is blocked by inhibitors of both Arp2/3 and formins. We propose that cyclic assembly of actin onto mitochondria modulates the fission/fusion balance, promotes network remodelling and content mixing, and thus may serve as an essential mechanism regulating mitochondrial network homeostasis.

Date: 2016
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DOI: 10.1038/ncomms12886

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