title: Involvement of Aif1 in apoptosis triggered by lack of Hxk2 in the yeast Saccharomyces cerevisiae.
abstract: We recently showed that in hxk2Δ cells, showing constitutive localization of active Ras at the mitochondria, addition of acetic acid caused an increase of both apoptotic and necrotic cells compared with the wild-type strain, providing a new role for hexokinase 2 (EC 2.7.1.1) as an anti-apoptotic factor, besides its known role as a glycolytic enzyme and as a regulator of gene transcription of several Mig1-regulated genes. We also demonstrated that apoptosis induced by lack of Hxk2 may not require the activation of Yca1. Here, we show that deletion of HXK2 causes hypersensitivity to H2O2 and that addition of this well-known apoptotic stimulus to hxk2Δ cells causes an increase in the level ROS, apoptosis and mitochondrial membrane potential. We also show that deletion of AIF1 in hxk2Δ cells enhances survival after induction of apoptosis with both H2O2 and acetic acid, rescues the reduction of both growth rate and cell size, abrogates both H2O2 and acetic acid-induced ROS accumulation and decreases cell death, suggesting that Aif1 might be involved in both H2O2 and acetic acid-induced cell death in hxk2Δ cells. Moreover, we show that active Ras proteins relocalize to the plasma membrane and to the nucleus in hxk2Δ aif1Δ cells.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, I-20126 Milan, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Amigoni
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, I-20126 Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Frigerio
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, I-20126 Milan, Italy SysBio Centre of Systems Biology, Piazza della Scienza 2, I-20126 Milan, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Martegani
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, I-20126 Milan, Italy SysBio Centre of Systems Biology, Piazza della Scienza 2, I-20126 Milan, Italy sonia.colombo@unimib.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Colombo
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D017209:Apoptosis; D017353:Gene Deletion; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D008564:Membrane Potentials; D051336:Mitochondrial Membranes / Q000502:physiology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; C443623:AIF1 protein, S cerevisiae; D009247:NADH, NADPH Oxidoreductases; C490214:HXK2 protein, S cerevisiae; D006593:Hexokinase; D019342:Acetic Acid
keywords: AIF1; HXK2; acetic acid; hydrogen peroxide; regulated cell death; yeast