Programmed cell death (PCD) in many systems is controlled by relative amounts of the apoptosis regulating proteins Bax and Bcl-2, through homo- or hetero-dimerization. Here we show that Bax-induced PCD of yeast was suppressed by transformation with a vesicle associated membrane protein from Arabidopsis (AtVAMP), which was isolated by screening a cDNA-expression library against sugar-induced-cell-death in yeast. AtVAMP expression blocked Bax-induced PCD downstream of oxidative burst. AtVAMP also prevented H2O2 induced apoptosis in yeast and in Arabidopsis cells. Reduced oxidation of lipids and of plasma membrane proteins were detected in the AtVAMP transformed yeast, suggesting improved membrane repair. Inhibition of intracellular vesicle trafficking by Brefeldin A induced apoptosis from sublethal concentration of H2O2. No protection occurred by overexpression of the yeast homolog SCN2. However, efficient suppression of yeast PCD occurred by expression of a chimera gene, composed of the conserved domains from yeast, fused to the variable N?terminal domain from Arabidopsis, resulting in exchange of the proline-rich N?terminal domain of SCN2 with a proline-poor Arabidopsis sequence. Our results suggest that intracellular vesicle traffic can regulate execution of apoptosis by affecting the rate of membrane recycling, and that the proline-rich N?terminal domain of VAMP inhibited this process.