Old yellow enzyme interferes with Bax-induced NADPH loss and lipid peroxidation in yeast

The yeast transcriptional response to murine Bax expression was compared with the changes induced by H2O2 treatment via microarray technology. Although most of the Bax-responsive genes were also triggered by H2O2 treatment, OYE3, ICY2, MLS1 and BTN2 were validated to have a Bax-specific transcriptional response not shared with the oxidative stress trigger. In knockout experiments, only deletion of OYE3, coding for yeast Old yellow enzyme, attenuated the rate of Bax-induced growth arrest, cell death and NADPH decrease. Lipid peroxidation was completely absent in ΔOYE3 expressing Bax. However, the absence of OYE3 sensitized yeast cells to H2O2-induced cell death, and increased the rate of NADPH decrease and lipid peroxidation. Our results clearly indicate that OYE3 interferes with Bax- and H2O2-induced lipid peroxidation and cell death in Saccharomyces cerevisiae.