Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis
Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis
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DOI：
10.1126/science.281.5385.2027
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发表时间：
1998-09-25
期刊：
影响因子：
56.9
通讯作者：
Kroemer, G
中科院分区：
文献类型：
--
作者：
Marzo, I;Brenner, C;Kroemer, G
促凋亡Bax蛋白通过作用于线粒体诱导细胞死亡。Bax与渗透性转换孔复合物（PTPC）结合，PTPC是一种参与线粒体膜渗透性调节的复合蛋白质通道。Bax从PTPC的免疫耗竭或纯化PTPC从β-缺陷小鼠产生的PTPC，不能透化膜响应于腺嘌呤核苷酸转运体（ANT）的促凋亡配体--腺苷酸。Bax和ANT在酵母双杂交系统中的免疫共沉淀和相互作用：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。重组Bax和纯化的ANT，但他们都没有单独，有效地形成在人工膜中的糖苷反应通道。因此，促凋亡分子Bax和组成性线粒体蛋白ANT在PTPC内合作以增加线粒体膜通透性并触发细胞死亡。
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.