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.
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