title: Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division.
abstract: During animal cell division, an actin-based ring cleaves the cell into two. Problems with this process can cause chromosome missegregation and defects in cytoplasmic inheritance and the partitioning of organelles, which in turn are associated with human diseases. Although much is known about how chromosome segregation is coupled to cell division, the way organelles coordinate their inheritance during partitioning to daughter cells is less well understood. Here, using a high-content live-imaging small interfering RNA screen, we identify Myosin-XIX (Myo19) as a novel regulator of cell division. Previously, this actin-based motor was shown to control the interphase movement of mitochondria. Our analysis shows that Myo19 is indeed localized to mitochondria and that its silencing leads to defects in the distribution of mitochondria within cells and in mitochondrial partitioning at division. Furthermore, many Myo19 RNAi cells undergo stochastic division failure--a phenotype that can be mimicked using a treatment that blocks mitochondrial fission and rescued by decreasing mitochondrial fusion, implying that mitochondria can physically interfere with cytokinesis. Strikingly, using live imaging we also observe the inappropriate movement of mitochondria to the poles of spindles in cells depleted for Myo19 as they enter anaphase. Since this phenocopies the results of an acute loss of actin filaments in anaphase, these data support a model whereby the Myo19 actin-based motor helps to control mitochondrial movement to ensure their faithful segregation during division. The presence of DNA within mitochondria makes their inheritance an especially important aspect of symmetrical cell division.
authors.affiliation: Centre for Clinical Science and Technology, Division of Medicine, University College London, Wolfson House, London NW1 2HE, UK. Electronic address: j.rohn@ucl.ac.uk.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rohn
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
authors.forename: Jigna V
authors.initials: JV
authors.lastname: Patel
authors.affiliation: Advanced Light Microscopy Facility, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Novo Nordisk Foundation Center for Protein Research, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Jutta
authors.initials: J
authors.lastname: Bulkescher
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
authors.forename: Nunu
authors.initials: N
authors.lastname: Mchedlishvili
authors.affiliation: Department of Biology, University of Richmond, Richmond, VA 23173, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: McMullan
authors.affiliation: Department of Biology, University of Richmond, Richmond, VA 23173, USA.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Quintero
authors.affiliation: Department of Cell Biology and Biophysics, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Ellenberg
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK. Electronic address: b.baum@ucl.ac.uk.
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
mesh_terms: D000199:Actins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D048749:Cytokinesis; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D009218:Myosins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; C548150:Myo19 protein, human; D009218:Myosins