title: Actin dynamics affect mitochondrial quality control and aging in budding yeast.
abstract: Actin cables of budding yeast are bundles of F-actin that extend from the bud tip or neck to the mother cell tip, serve as tracks for bidirectional cargo transport, and undergo continuous movement from buds toward mother cells [1]. This movement, retrograde actin cable flow (RACF), is similar to retrograde actin flow in lamellipodia, growth cones, immunological synapses, dendritic spines, and filopodia [2-5]. In all cases, actin flow is driven by the push of actin polymerization and assembly at the cell cortex, and myosin-driven pulling forces deeper within the cell [6-10]. Therefore, for movement and inheritance from mothers to buds, mitochondria must "swim upstream" against the opposing force of RACF [11]. We find that increasing RACF rates results in increased fitness of mitochondria inherited by buds and that the increase in mitochondrial fitness leads to extended replicative lifespan and increased cellular healthspan. The sirtuin SIR2 is required for normal RACF and mitochondrial fitness, and increasing RACF rates in sir2Δ cells increases mitochondrial fitness and cellular healthspan but does not affect replicative lifespan. These studies support the model that RACF serves as a filter for segregation of fit from less-fit mitochondria during inheritance, which controls cellular lifespan and healthspan. They also support a role for Sir2p in these processes.
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 W. 168(th) Street, New York, NY 10032, USA.
authors.forename: Ryo
authors.initials: R
authors.lastname: Higuchi
authors.forename: Jason D
authors.initials: JD
authors.lastname: Vevea
authors.forename: Theresa C
authors.initials: TC
authors.lastname: Swayne
authors.forename: Robert
authors.initials: R
authors.lastname: Chojnowski
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hill
authors.forename: Istvan R
authors.initials: IR
authors.lastname: Boldogh
authors.forename: Liza A
authors.initials: LA
authors.lastname: Pon
mesh_terms: D000199:Actins / Q000235:genetics; D000375:Aging / Q000235:genetics*; D060049:Asymmetric Cell Division; D001692:Biological Transport; D019070:Cell Lineage; D002470:Cell Survival / Q000235:genetics; D048749:Cytokinesis; D017353:Gene Deletion; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000096:biosynthesis / Q000235:genetics*; D056565:Sirtuin 2 / Q000096:biosynthesis / Q000235:genetics*; D014335:Tropomyosin / Q000235:genetics
chemical_list: D000199:Actins; C112936:MYO1 protein, S cerevisiae; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014335:Tropomyosin; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D018995:Myosin Heavy Chains