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.