An AIF orthologue regulates apoptosis in yeast |
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Authors: | Wissing Silke Ludovico Paula Herker Eva Büttner Sabrina Engelhardt Silvia M Decker Thorsten Link Alexander Proksch Astrid Rodrigues Fernando Corte-Real Manuela Fröhlich Kai-Uwe Manns Joachim Candé Céline Sigrist Stephan J Kroemer Guido Madeo Frank |
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Affiliation: | Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Strasse 4, Tuebingen 72076, Germany. |
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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). |
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Keywords: | apoptosis-inducing factor YNR074C YCA1 cyclophilin A aging |
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