title: Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission.
abstract: In addition to established membrane remodeling roles in various cellular locations, actin has recently emerged as a participant in mitochondrial fission. However, the underlying mechanisms of its participation remain largely unknown. We report that transient de novo F-actin assembly on the mitochondria occurs upon induction of mitochondrial fission and F-actin accumulates on the mitochondria without forming detectable submitochondrial foci. Impairing mitochondrial division through Drp1 knockout or inhibition prolonged the time of mitochondrial accumulation of F-actin and also led to abnormal mitochondrial accumulation of the actin regulatory factors cortactin, cofilin, and Arp2/3 complexes, suggesting that disassembly of mitochondrial F-actin depends on Drp1 activity. Furthermore, down-regulation of actin regulatory proteins led to elongation of mitochondria, associated with mitochondrial accumulation of Drp1. In addition, depletion of cortactin inhibited Mfn2 down-regulation- or FCCP-induced mitochondrial fragmentation. These data indicate that the dynamic assembly and disassembly of F-actin on the mitochondria participates in Drp1-mediated mitochondrial fission.
authors.affiliation: Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Sunan
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Roelofs
authors.affiliation: Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Liron
authors.initials: L
authors.lastname: Boyman
authors.affiliation: Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: W Jonathan
authors.initials: WJ
authors.lastname: Lederer
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.affiliation: Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 Center for Biomedical Engineering and Technology, Department of Biochemistry and Molecular Biology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201 mkarbowski@umaryland.edu.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Karbowski
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D051356:Cortactin / Q000235:genetics / Q000378:metabolism; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D063154:Mitochondrial Dynamics / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D008938:Mitosis; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D051339:Actin Depolymerizing Factors; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D051356:Cortactin; C495869:Cttn protein, mouse; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins