The Mitochondrial F0F1-ATPase proton pump is required for function of the proapoptotic protein Bax in yeast and mammalian cells.
The proapoptotic mammalian protein Bax associates with mitochondrial membranes and confers a lethal phenotype when expressed in yeast. By generating Bax-resistant mutant yeast and using classical complementation cloning methods, subunits of the mitochondrial F0F1-ATPase proton pump were determined to be critical for Bax-mediated killing in S. cerevisiae. A pharmacological inhibitor of the proton pump, oligomycin, also partially abrogated the cytotoxic actions of Bax in yeast. In mammalian cells, oligomycin also inhibited Bax-induced apoptosis and activation of cell death proteases. The findings imply that an intact F0F1-ATPase in the inner membrane of mitochondria is necessary for optimal function of Bax in both yeast and mammalian cells.
Matsuyama
S
S
Burnham Institute, Program on Apoptosis and Cell Death Research La Jolla, California 92037, USA.
Xu
Q
Q
Velours
J
J
Reed
J C
JC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005057:Eukaryotic Cells / Q000201:enzymology; D005800:Genes, Fungal / Q000502:physiology; D005816:Genetic Complementation Test; D007668:Kidney / Q000166:cytology; D008322:Mammals; D009154:Mutation / Q000502:physiology; D009840:Oligomycins / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D009840:Oligomycins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014475:Uncoupling Agents; D051028:bcl-2-Associated X Protein; D006180:Proton-Translocating ATPases