Antagonistic roles of old yellow enzymes (OYE) in oxidative stress and programmed cell death in yeast
Odat, O. S.
Apoptosis is a highly regulated form of programmed cell death, which was thought to be found only in mammalian cells. The recent discovery of apoptotic markers in S. cerevisiae also pointed to the presence of the basic mechanisms of apoptosis in unicellular eukaryotes. This evidence was strengthened by the discovery of several yeast analogues of the apoptosis machinery components (yAIF. AMID,Htra). The Old Yellow Enzyme (OYE) group of FMN-oxidoreductases has received extensive attention over the years from biochemists for their catalytic properties. NADPH was found to be the physiological reductant of this enzyme. Previous work, employing a genetic screening for proteins modulating Bax lethality showed that the C-terminus of OYE2 restores Bax lethality acting as a dominant negative. Whereas the full length OYE2 suppress Bax lethality. Additionally study showed that the OYE3 gene, a highly related homologue of OYE2 with 82% identity at the amino acid levels, is also implicated negatively in the Bax phenotype. Overexpressing OYE2 lowered the endogenous levels of ROS, whereas overexpressing OYE3 produced higher levels of ROS compared to the control cells. When treating logarithmically growing cultures with H2O2 the cultures overexpressing OYE2 recover faster than the control cells, while cultures overexpressing OYE3 fail to recover. Surprisingly, the (delta)oye2 oye3 double knockout showed higher resistance to H2O2 induced PCD than the single knockouts or the control, and reduced cell death during chronological aging. And a slightly lower ROS levels than the control cells with and without H2O2 treatment.
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