title: Ysp2 mediates death of yeast induced by amiodarone or intracellular acidification.
abstract: Recently we have found that the drug amiodarone induces apoptosis in yeast, which is mediated by reactive oxygen species (ROS). Here we have used this finding as a tool to screen for genes involved in the death program. We have described a novel mitochondrial protein, Ysp2, acting in the amiodarone-induced death cascade. After amiodarone addition both the control and amiodarone-resistant ysp2-deleted cells formed ROS, but the mutant (unlike the control) did not undergo the mitochondrial thread-to-grain transition. To test whether the action of Ysp2 is amiodarone-specific we tried to induce PCD by other agents. We have found that acetic acid-induced PCD also depends on Ysp2. We also demonstrate that, like acetic acid, propionic acid or nigericin triggered intracellular acidification causing ROS-dependent death. We suggest that intracellular acidification results in the protonation of superoxide anion (O2-*) to form HO2, one of the most aggressive ROS, which in turn induces Ysp2-mediated PCD.
authors.affiliation: Molecular Biology Department, Faculty of Biology, Lomonosov Moscow State University, Moscow 119899, Russia.
authors.forename: Sviatoslav
authors.initials: S
authors.lastname: Sokolov
authors.forename: Dmitry
authors.initials: D
authors.lastname: Knorre
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Smirnova
authors.forename: Olga
authors.initials: O
authors.lastname: Markova
authors.forename: Andrey
authors.initials: A
authors.lastname: Pozniakovsky
authors.forename: Vladimir
authors.initials: V
authors.lastname: Skulachev
authors.forename: Fedor
authors.initials: F
authors.lastname: Severin
mesh_terms: D019342:Acetic Acid / Q000378:metabolism*; D000638:Amiodarone / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C515231:Ysp2 protein, S cerevisiae; D000638:Amiodarone; D019342:Acetic Acid