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Updated: Jul 20, 2026

Manipulation and Analysis of Cell Cycle-Dependent Processes in Budding Yeast
Published on: September 26, 2025
Ysp2 mediates death of yeast induced by amiodarone or intracellular acidification
Sviatoslav Sokolov1, Dmitry Knorre, Ekaterina Smirnova
1Molecular Biology Department, Faculty of Biology, Lomonosov Moscow State University, Moscow 119899, Russia.
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.
Insights
A novel protein, Ysp2, is crucial for programmed cell death (PCD) in yeast, triggered by amiodarone and intracellular acidification. This discovery sheds light on reactive oxygen species (ROS) mediated cell death pathways.
Area of Science:
- Cell Biology
- Biochemistry
- Genetics
Background:
- Amiodarone induces apoptosis in yeast via reactive oxygen species (ROS).
- This study screens for genes involved in the amiodarone-induced cell death pathway.
- Identifies a novel mitochondrial protein, Ysp2, in this cascade.
Purpose of the Study:
- To identify genes involved in amiodarone-induced programmed cell death (PCD).
- To characterize the function of the novel mitochondrial protein Ysp2 in cell death.
- To investigate if Ysp2's role in PCD is specific to amiodarone or extends to other death-inducing agents.
Main Methods:
- Yeast genetics: screening of ysp2-deleted mutants for amiodarone resistance.
- Mitochondrial morphology analysis: observing the thread-to-grain transition.
- Induction of PCD using various agents: acetic acid, propionic acid, and nigericin.
- ROS level measurement.
Main Results:
- Ysp2 deletion confers resistance to amiodarone-induced PCD, despite ROS production.
- Ysp2 is essential for the mitochondrial thread-to-grain transition during amiodarone-induced death.
- Ysp2-mediated PCD is also induced by intracellular acidification (acetic acid, propionic acid, nigericin).
- Intracellular acidification leads to increased ROS, specifically HO2, promoting Ysp2-mediated PCD.
Conclusions:
- The mitochondrial protein Ysp2 plays a critical role in yeast PCD.
- Ysp2-mediated PCD is triggered by both amiodarone and intracellular acidification.
- ROS, particularly HO2 generated during acidification, are key mediators of Ysp2-dependent cell death.
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