An AIF orthologue regulates apoptosis in yeast.
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).
Wissing
Silke
S
Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, Tuebingen 72076, Germany.
Ludovico
Paula
P
Herker
Eva
E
Büttner
Sabrina
S
Engelhardt
Silvia M
SM
Decker
Thorsten
T
Link
Alexander
A
Proksch
Astrid
A
Rodrigues
Fernando
F
Corte-Real
Manuela
M
Fröhlich
Kai-Uwe
KU
Manns
Joachim
J
Candé
Céline
C
Sigrist
Stephan J
SJ
Kroemer
Guido
G
Madeo
Frank
F
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
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