Ysp2 mediates death of yeast induced by amiodarone or intracellular acidification.
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.
Sokolov
Sviatoslav
S
Molecular Biology Department, Faculty of Biology, Lomonosov Moscow State University, Moscow 119899, Russia.
Knorre
Dmitry
D
Smirnova
Ekaterina
E
Markova
Olga
O
Pozniakovsky
Andrey
A
Skulachev
Vladimir
V
Severin
Fedor
F
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*
D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C515231:Ysp2 protein, S cerevisiae; D000638:Amiodarone; D019342:Acetic Acid