Knock-out of metacaspase and/or cytochrome c results in the activation of a ROS-independent acetic acid-induced programmed cell death pathway in yeast

Abstract 

To gain further insight into yeast acetic acid-induced programmed cell death (AA-PCD) we analyzed the effects of the antioxidant N-acetyl-l-cysteine (NAC) on cell viability, hydrogen peroxide (H₂O₂) production, DNA fragmentation, cytochrome c (cyt c) release and caspase-like activation in wild type (wt) and metacaspase and/or cyt c-lacking cells. We found that NAC prevents AA-PCD in wt cells, by scavenging H₂O₂ and by inhibiting both cyt c release and caspase-like activation. This shows the occurrence of a reactive oxygen species (ROS)-dependent AA-PCD. Contrarily no NAC dependent change in AA-PCD of mutant cells was detectable, showing that a ROS-independent AA-PCD can also occur.

Keywords: Yeast, Programmed cell death, Reactive oxygen species, N-Acetyl-l-cysteine, Cytochrome c, YCA1

Abbreviations: ROS, reactive oxygen species, AA, acetic acid, PCD, programmed cell death, AA-PCD, acetic acid-induced programmed cell death, NAC, N-acetyl-l-cysteine, wt, wild type, Δcyc1,7, CYC1 and CYC7-lacking, H₂O₂, hydrogen peroxide, cyt c, cytochrome c, DCF, dichlorofluorescein diacetate