Matsuyama S, Xu Q, Velours J, Reed J C
Burnham Institute, Program on Apoptosis and Cell Death Research La Jolla, California 92037, USA.
Mol Cell. 1998 Feb;1(3):327-36. doi: 10.1016/s1097-2765(00)80033-7.
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.
促凋亡的哺乳动物蛋白Bax与线粒体膜结合，在酵母中表达时会赋予致死表型。通过产生抗Bax的突变酵母并使用经典的互补克隆方法，线粒体F0F1 - ATP合酶质子泵的亚基被确定为对酿酒酵母中Bax介导的杀伤至关重要。质子泵的药理学抑制剂寡霉素也部分消除了Bax在酵母中的细胞毒性作用。在哺乳动物细胞中，寡霉素也抑制Bax诱导的细胞凋亡和细胞死亡蛋白酶的激活。这些发现表明，线粒体内膜中完整的F0F1 - ATP合酶对于Bax在酵母和哺乳动物细胞中的最佳功能是必需的。
