THE MITOCHONDRIAL F0F1-ATPASE PROTON PUMP IS REQUIRED FOR FUNCTION OFTHE PROAPOPTOTIC PROTEIN BAX IN YEAST AND MAMMALIAN-CELLS

The proapoptotic mammalian protein Bar associates with mitochondrial m embranes and confers a lethal phenotype when expressed in yeast. By ge nerating Bax-resistant mutant yeast and using classical complementatio n cloning methods, subunits of the mitochondrial F0F1-ATPase proton pu mp were determined to be critical for Bax-mediated killing in S. cerev isiae. A pharmacological inhibitor of the proton pump, oligomycin, als o partially abrogated the cytotoxic actions of Bax in yeast. In mammal ian cells, oligomycin also inhibited Bax-induced apoptosis and activat ion of cell death proteases. The findings imply that an intact F0F1-AT Pase in the inner membrane of mitochondria is necessary for optimal fu nction of Bax in both yeast and mammalian cells.