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An AIF orthologue regulates apoptosis in yeast

¹ Institute for Physiological Chemistry, ² Department of Internal Medicine I, University of Tübingen, 72076 Tübingen, Germany
³ Life and Health Sciences Research Institute, Health Sciences School, ⁴ Department of Biology, School of Sciences, University of Minho, 4710-057 Braga, Portugal
⁵ IMBM, University of Graz, 8010 Graz, Austria
⁶ CNRS-UMR8125, Institut Gustave Roussy, F-94805 Villejuif, France
⁷ European Neuroscience Institute Göttingen, Max-Planck-Society, 37073 Göttingen, Germany

Address correspondence to Frank Madeo, Institute for Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Str. 4, Tuebingen 72076 Germany. Tel.: 49-7071-2974184. Fax: 49-7071-295565. email: frank.madeo{at}uni-tuebingen.de

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).

Key Words: apoptosis-inducing factor; YNR074C; YCA1; cyclophilin A; aging

M. Corte-Real and F. Madeo contributed equally to this paper.

Abbreviations used in this paper: AIF, apoptosis-inducing factor; CypA, cyclophilin A.

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