Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites

  1. Wei-ke Ji
  2. Anna L Hatch
  3. Ronald A Merrill
  4. Stefan Strack
  5. Henry N Higgs  Is a corresponding author
  1. Geisel School of Medicine at Dartmouth, United States
  2. The University of Iowa, United States

Abstract

While the dynamin GTPase Drp1 plays a critical role during mitochondrial fission, mechanisms controlling its recruitment to fission sites are unclear. A current assumption is that cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Using live-cell microscopy, we find evidence for a different model, progressive maturation of Drp1 oligomers on mitochondria through incorporation of smaller mitochondrially-bound Drp1 units. Maturation of a stable Drp1 oligomer does not forcibly lead to fission. Inhibiting actin polymerization, myosin IIA, or the formin INF2 reduces both un-stimulated and ionomycin-induced Drp1 accumulation and mitochondrial fission. Actin filaments bind purified Drp1 and increase GTPase activity in a manner that is synergistic with the mitochondrial protein Mff, suggesting a role for direct Drp1/actin interaction. We propose that Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and that fission factors such as actin filaments target productive oligomerization to fission sites.

Article and author information

Author details

  1. Wei-ke Ji

    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Anna L Hatch

    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ronald A Merrill

    Department of Pharmacology, The University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Stefan Strack

    Department of Pharmacology, The University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Henry N Higgs

    Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
    For correspondence
    henry.higgs@dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Pekka Lappalainen, University of Helsinki, Finland

Publication history

  1. Received: September 11, 2015
  2. Accepted: November 25, 2015
  3. Accepted Manuscript published: November 26, 2015 (version 1)
  4. Accepted Manuscript updated: November 30, 2015 (version 2)
  5. Version of Record published: February 3, 2016 (version 3)

Copyright

© 2015, Ji et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Wei-ke Ji
  2. Anna L Hatch
  3. Ronald A Merrill
  4. Stefan Strack
  5. Henry N Higgs
(2015)
Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites
eLife 4:e11553.
https://doi.org/10.7554/eLife.11553

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