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

Wei-ke Ji; Anna L Hatch; Ronald A Merrill; Stefan Strack; Henry N Higgs

doi:10.7554/eLife.11553

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

Journal article

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

Wei-ke Ji, Anna L Hatch, Ronald A Merrill, Stefan Strack and Henry N Higgs

eLife, Vol.4(2015), pp.e11553-e11553

11/26/2015

DOI: 10.7554/eLife.11553

PMCID: PMC4755738

PMID: 26609810

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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. Drp1 oligomers also translocate directionally along mitochondria. Ionomycin, a calcium ionophore, causes rapid mitochondrial accumulation of actin filaments followed by Drp1 accumulation at the fission site, and increases fission rate. 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.

Mitochondrial Dynamics

Cell Line

Actin Cytoskeleton - metabolism

GTP Phosphohydrolases - metabolism

Microtubule-Associated Proteins - metabolism

Mitochondrial Proteins - metabolism

Humans

Protein Multimerization

Protein Binding

Protein Transport

Details

Title: Subtitle: Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites
Creators: Wei-ke Ji - Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
Anna L Hatch - Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
Ronald A Merrill - Department of Pharmacology, The University of Iowa, Iowa City, United States
Stefan Strack - Department of Pharmacology, The University of Iowa, Iowa City, United States
Henry N Higgs - Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, United States
Resource Type: Journal article
Publication Details: eLife, Vol.4(2015), pp.e11553-e11553
DOI: 10.7554/eLife.11553
PMID: 26609810
PMCID: PMC4755738
NLM abbreviation: Elife
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: England
Grant note: GM106000 / NIGMS NIH HHS R01 DK088826 / NIDDK NIH HHS NS087908 / NINDS NIH HHS S10 OD010330 / NIH HHS R56 NS056244 / NINDS NIH HHS R21 NS087908 / NINDS NIH HHS DK088826 / NIDDK NIH HHS P30 CA023108 / NCI NIH HHS R01 GM106000 / NIGMS NIH HHS S10OD010330 / NIH HHS R01 GM069818 / NIGMS NIH HHS GM069818 / NIGMS NIH HHS R01 NS056244 / NINDS NIH HHS NS056244 / NINDS NIH HHS
Language: English
Date published: 11/26/2015
Academic Unit: Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040211602771

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