title: An AIF orthologue regulates apoptosis in yeast.
abstract: Apoptosis-inducing factor (AIF), a key regulator of cell death, is essential for normal mammalian development and participates in pathological apoptosis. The proapoptotic nature of AIF and its mode of action are controversial. Here, we show that the yeast AIF homologue Ynr074cp controls yeast apoptosis. Similar to mammalian AIF, Ynr074cp is located in mitochondria and translocates to the nucleus of yeast cells in response to apoptotic stimuli. Purified Ynr074cp degrades yeast nuclei and plasmid DNA. YNR074C disruption rescues yeast cells from oxygen stress and delays age-induced apoptosis. Conversely, overexpression of Ynr074cp strongly stimulates apoptotic cell death induced by hydrogen peroxide and this effect is attenuated by disruption of cyclophilin A or the yeast caspase YCA1. We conclude that Ynr074cp is a cell death effector in yeast and rename it AIF-1 (Aif1p, gene AIF1).
authors.affiliation: Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, Tuebingen 72076, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Wissing
authors.forename: Paula
authors.initials: P
authors.lastname: Ludovico
authors.forename: Eva
authors.initials: E
authors.lastname: Herker
authors.forename: Sabrina
authors.initials: S
authors.lastname: Büttner
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Engelhardt
authors.forename: Thorsten
authors.initials: T
authors.lastname: Decker
authors.forename: Alexander
authors.initials: A
authors.lastname: Link
authors.forename: Astrid
authors.initials: A
authors.lastname: Proksch
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues
authors.forename: Manuela
authors.initials: M
authors.lastname: Corte-Real
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Fröhlich
authors.forename: Joachim
authors.initials: J
authors.lastname: Manns
authors.forename: Céline
authors.initials: C
authors.lastname: Candé
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D021984:Cyclophilin A / Q000037:antagonists & inhibitors / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005420:Flavoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D005420:Flavoproteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D006861:Hydrogen Peroxide; C443623:AIF1 protein, S cerevisiae; D009247:NADH, NADPH Oxidoreductases; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; D021984:Cyclophilin A