The redox-sensing quinone reductase Lot6p acts as an inducer of yeast apoptosis.
Mammalian NAD(P)H:quinone oxidoreductases such as human NQO1 act as inducers of apoptosis. Quinone reductases generated interest over the last decade due to their proposed function in the oxidative stress response. Furthermore, human NQO1 was reported to regulate p53 stability and p53-dependent apoptosis through regulation of cellular oxidation-reduction events. In this study, we have used low concentrations of hydrogen peroxide (0.4 and 0.6 mM) to induce apoptosis-like cell death in wild type, an LOT6 overexpressing and a Deltalot6 yeast strain to monitor cell survival. Using this approach, we demonstrate that yeast quinone reductase Lot6p, an orthologue of mammalian quinone reductases, plays a pivotal role in apoptosis-like cell death in Saccharomyces cerevisiae. Overexpression of LOT6 results in enhanced cell death, as shown by an investigation of the morphological hallmarks of apoptosis-like fragmentation of DNA and externalization of phosphatidylserine, whereas the deletion strain displays a deficiency in apoptosis-like cell death as compared with the wild type. Thus, we propose that Lot6p is directly involved in the control of the apoptosis-like cell death in yeast.
Sollner
Sonja
S
Institute of Biochemistry, Graz University of Technology, Graz, Austria. sonja.sollner@imp.ac.at
Durchschlag
Michael
M
Fröhlich
Kai-Uwe
KU
Macheroux
Peter
P
D017209:Apoptosis; D002462:Cell Membrane / Q000737:chemistry; D053938:DNA Fragmentation; D038181:FMN Reductase / Q000502:physiology*; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000502:physiology; D010084:Oxidation-Reduction; D010718:Phosphatidylserines / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D013312:Stress, Physiological
D010718:Phosphatidylserines; D029701:Saccharomyces cerevisiae Proteins; D038181:FMN Reductase; C490376:LOT6 protein, S cerevisiae; D016660:NAD(P)H Dehydrogenase (Quinone)