title: Active segregation of yeast mitochondria by Myo2 is essential and mediated by Mmr1 and Ypt11.
abstract: Active segregation of essential organelles is required for successful cell division. The essential budding yeast myosin V Myo2 actively segregates most organelles along polarized actin cables. The mechanism of mitochondrial segregation remains controversial, with movement driven by actin polymerization, movement driven by association with transported cortical endoplasmic reticulum (ER), and direct transport by Myo2 proposed as models. Two nonessential proteins, Mmr1 and the Rab GTPase Ypt11, bind Myo2 and have been implicated in mitochondrial inheritance, although their specific roles are also contended. We generated myo2(sens) mutations that exhibit no overt phenotype but render MMR1 essential and have compromised Ypt11 binding. We then isolated myo2(sens)mmr1(ts) conditional mutants and determined that they have a specific and severe defect in active mitochondrial inheritance, revealing mitochondrial transport by Myo2 as an essential function. ypt11Δ mmr1(ts) cells also have conditional defects in growth and active transport of mitochondria into the bud, both of which are suppressed by artificially forcing mitochondrial inheritance. At the restrictive temperature, cells defective in mitochondrial inheritance give rise to dead buds that go through cytokinesis normally, showing no evidence of a proposed cell-cycle mitochondrial inheritance checkpoint. Thus, active mitochondrial inheritance is an essential process and a function of Myo2 that requires either Mmr1 or Ypt11.
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Weill Hall, Cornell University, Ithaca, NY 14850, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Chernyakov
authors.forename: Felipe
authors.initials: F
authors.lastname: Santiago-Tirado
authors.forename: Anthony
authors.initials: A
authors.lastname: Bretscher
mesh_terms: D016764:Cell Polarity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050259:Genes, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004718:Saccharomycetales / Q000378:metabolism / Q000648:ultrastructure*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D018995:Myosin Heavy Chains; D020691:rab GTP-Binding Proteins