Viral killer toxins induce caspase-mediated apoptosis in yeast.
In yeast, apoptotic cell death can be triggered by various factors such as H2O2, cell aging, or acetic acid. Yeast caspase (Yca1p) and cellular reactive oxygen species (ROS) are key regulators of this process. Here, we show that moderate doses of three virally encoded killer toxins (K1, K28, and zygocin) induce an apoptotic yeast cell response, although all three toxins differ significantly in their primary killing mechanisms. In contrast, high toxin concentrations prevent the occurrence of an apoptotic cell response and rather cause necrotic, toxin-specific cell killing. Studies with Deltayca1 and Deltagsh1 deletion mutants indicate that ROS accumulation as well as the presence of yeast caspase 1 is needed for apoptosis in toxin-treated yeast cells. We conclude that in the natural environment of toxin-secreting killer yeasts, where toxin concentration is usually low, induction of apoptosis might play an important role in efficient toxin-mediated cell killing.
Reiter
Jochen
J
Applied Molecular Biology, University of the Saarland, D-66041 Saarbrücken, Germany.
Herker
Eva
E
Madeo
Frank
F
Schmitt
Manfred J
MJ
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000502:physiology; D020287:In Situ Nick-End Labeling; D055646:Killer Factors, Yeast; D009183:Mycotoxins / Q000494:pharmacology / Q000502:physiology; D009336:Necrosis / Q000139:chemically induced; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000494:pharmacology* / Q000502:physiology
C089359:K1 killer toxin; C527157:KHR1 protein, S cerevisiae; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D017361:Viral Nonstructural Proteins; C470739:zygocin protein, Zygosaccharomyces bailii virus M; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; C490862:GSH1 protein, S cerevisiae; D005721:Glutamate-Cysteine Ligase