Marzo I, Brenner C, Zamzami N, Jürgensmeier J M, Susin S A, Vieira H L, Prévost M C, Xie Z, Matsuyama S, Reed J C, Kroemer G
CNRS, UPR 420, 19 rue Guy Môquet, F-94801 Villejuif, France.
Science. 1998 Sep 25;281(5385):2027-31. doi: 10.1126/science.281.5385.2027.
The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nucleotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.
促凋亡蛋白Bax通过作用于线粒体诱导细胞死亡。Bax与通透性转换孔复合体（PTPC）结合，PTPC是一种复合蛋白质通道，参与线粒体膜通透性的调节。从PTPC中免疫去除Bax或从Bax缺陷小鼠中纯化PTPC，得到的PTPC对腺嘌呤核苷酸转位酶（ANT）的促凋亡配体阿托伐醌不产生膜通透性反应。Bax和ANT在酵母双杂交系统中共免疫沉淀并相互作用。Bax的异位表达在野生型酵母中诱导细胞死亡，但在ANT缺陷型酵母中不诱导细胞死亡。重组Bax和纯化的ANT单独都不能有效地在人工膜中形成对阿托伐醌有反应的通道，但两者共同作用则可以。因此，促凋亡分子Bax和组成型线粒体蛋白ANT在PTPC内协同作用，增加线粒体膜通透性并触发细胞死亡。
