title: Mitochondrial anchorage and fusion contribute to mitochondrial inheritance and quality control in the budding yeast Saccharomyces cerevisiae.
abstract: Higher-functioning mitochondria that are more reduced and have less ROS are anchored in the yeast bud tip by the Dsl1-family protein Mmr1p. Here we report a role for mitochondrial fusion in bud-tip anchorage of mitochondria. Fluorescence loss in photobleaching (FLIP) and network analysis experiments revealed that mitochondria in large buds are a continuous reticulum that is physically distinct from mitochondria in mother cells. FLIP studies also showed that mitochondria that enter the bud can fuse with mitochondria that are anchored in the bud tip. In addition, loss of fusion and mitochondrial DNA (mtDNA) by deletion of mitochondrial outer or inner membrane fusion proteins (Fzo1p or Mgm1p) leads to decreased accumulation of mitochondria at the bud tip and inheritance of fitter mitochondria by buds compared with cells with no mtDNA. Conversely, increasing the accumulation and anchorage of mitochondria in the bud tip by overexpression of MMR1 results in inheritance of less-fit mitochondria by buds and decreased replicative lifespan and healthspan. Thus quantity and quality of mitochondrial inheritance are ensured by two opposing processes: bud-tip anchorage by mitochondrial fusion and Mmr1p, which favors bulk inheritance; and quality control mechanisms that promote segregation of fitter mitochondria to the bud.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Ryo
authors.initials: R
authors.lastname: Higuchi-Sanabria
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Charalel
authors.affiliation: Department of Developmental and Cell Biology and Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697.
authors.forename: Matheus P
authors.initials: MP
authors.lastname: Viana
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Garcia
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Cierra N
authors.initials: CN
authors.lastname: Sing
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Andrea
authors.initials: A
authors.lastname: Koenigsberg
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032.
authors.forename: Theresa C
authors.initials: TC
authors.lastname: Swayne
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Vevea
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
authors.forename: Istvan R
authors.initials: IR
authors.lastname: Boldogh
authors.affiliation: Department of Developmental and Cell Biology and Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Rafelski
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032 lap5@cumc.columbia.edu.
authors.forename: Liza A
authors.initials: LA
authors.lastname: Pon
mesh_terms: D004272:DNA, Mitochondrial / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D038761:Photobleaching; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C082883:MGM1 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C571177:Mmr1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C094774:DNM1 protein, S cerevisiae