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
Reviewing Editor
- Pekka Lappalainen, University of Helsinki, Finland
Publication history
- Received: September 11, 2015
- Accepted: November 25, 2015
- Accepted Manuscript published: November 26, 2015 (version 1)
- Accepted Manuscript updated: November 30, 2015 (version 2)
- 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.
Metrics
-
- 5,460
- Page views
-
- 1,567
- Downloads
-
- 116
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.