Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a classical glycolytic enzyme, is involved in cellular energy production and has important housekeeping functions. In this report, we show that a GAPDH from Arabidopsis, GAPDHa, has a novel function involved in H(2)O(2)-mediated cell death in yeast and Arabidopsis protoplasts. GAPDHa was cloned along with other plant genes that suppress Bax-induced cell death in yeast. Flow cytometry analyses with dihydrorhodamine 123 indicated that H(2)O(2) production mediated by Bax expression in yeast cells was greatly reduced when Bax was coexpressed with GAPDHa. In plants, GAPDHa transcript levels were greatly increased by H(2)O(2) treatment. Furthermore, transformation of GAPDHa into Arabidopsis protoplasts strongly suppressed heat shock-induced H(2)O(2) production and cell death. Together, our results indicate that GAPDH controls generation of H(2)O(2) by Bax and heat shock, which in turn suppresses cell death in yeast and plant cells.