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.

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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