The mechanism by which the proapoptotic protein Bax exerts its effects has not been clear, although it is thought to involve alterations in mitochondrial physiology. Harris et al. report one possible reason why Bax expression is toxic in both yeast and mammalian cells. Analysis of respiration-incompetent yeast with specific deletions in the electron transport chain and the machinery of mitochondrial ATP synthesis indicated that the ability to respire is critical for Bax toxicity. Bax expression did not impair growth in these mutants as compared with wild-type cells. However, Bax toxicity was increased in a respiratory-competent yeast strain that lacked voltage-dependent anion channel (VDAC). The authors propose that Bax may impair oxidative phosphorylation and that VDAC may act to limit this effect. Harris, M.H., Vander Heiden, M.G., Kron, S.J., and Thompson, C.B. (2000) Role of oxidative phosphorylation in Bax toxicity. Mol. Cell. Biol. 20 : 3590-3596. [Abstract] [Full Text]