title: Functional mitochondria are required for alpha-synuclein toxicity in aging yeast.
abstract: alpha-Synuclein is one of the principal toxic triggers of Parkinson disease, an age-associated neurodegeneration. Using old yeast as a model of alpha-synuclein expression in post-mitotic cells, we show that alpha-synuclein toxicity depends on chronological aging and results in apoptosis as well as necrosis. Neither disruption of key components of the unfolded protein response nor deletion of proapoptotic key players (including the yeast caspase YCA1, the apoptosis-inducing factor AIF1, or the serine protease OMI) did prevent alpha-synuclein-induced cell killing. However, abrogation of mitochondrial DNA (rho(0)) inhibited alpha-synuclein-induced reactive oxygen species formation and subsequent apoptotic cell death. Thus, introducing an aging yeast model of alpha-synuclein toxicity, we demonstrate a strict requirement of functional mitochondria.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Büttner
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bitto
authors.forename: Julia
authors.initials: J
authors.lastname: Ring
authors.forename: Manuela
authors.initials: M
authors.lastname: Augsten
authors.forename: Piotr
authors.initials: P
authors.lastname: Zabrocki
authors.forename: Tobias
authors.initials: T
authors.lastname: Eisenberg
authors.forename: Helmut
authors.initials: H
authors.lastname: Jungwirth
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hutter
authors.forename: Didac
authors.initials: D
authors.lastname: Carmona-Gutierrez
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology*; D000074923:High-Temperature Requirement A Serine Peptidase 2; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D051844:alpha-Synuclein; C443623:AIF1 protein, S cerevisiae; D009247:NADH, NADPH Oxidoreductases; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2; D020169:Caspases; C456272:MCA1 protein, S cerevisiae