Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis.
Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis.
复制标题
腺嘌呤核苷酸易位酶-1是渗透性过渡孔的成分，可以主要诱导凋亡。
DOI：
10.1083/jcb.147.7.1493
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发表时间：
1999-12-27
影响因子：
7.8
通讯作者：
Grimm, S
中科院分区：
文献类型：
--
作者：
Bauer, M K;Schubert, A;Rocks, O;Grimm, S
在这里，我们描述了分离的腺嘌呤核苷酸转位酶-1（ANT-1）在屏幕上占主导地位的，诱变基因。ANT-1是线粒体渗透性转换复合物的一种组分，线粒体渗透性转换复合物是一种连接线粒体内膜与外膜的蛋白质聚集体，最近被认为与细胞凋亡有关。ANT-1表达导致细胞凋亡的所有特征，例如表型改变、线粒体膜电位的崩溃、细胞色素c释放、半胱天冬酶激活和DNA降解。这两个点突变，损害ANT-1在其已知的活动，运输ADP和ATP，以及NH 2-末端的一半蛋白质仍然可以诱导细胞凋亡。有趣的是，ANT-2，一个高度同源的蛋白不能导致细胞死亡，证明了细胞凋亡诱导信号的特异性。与Bax（一种促凋亡Bcl-2基因）相反，ANT-1在酵母中不能引起某种形式的细胞死亡。这和观察到的ANT-1相互作用蛋白亲环素D对细胞凋亡的抑制表明ANT-1的自杀作用是由渗透性转换孔内的特异性蛋白质-蛋白质相互作用介导的。
Here, we describe the isolation of adenine nucleotide translocase-1 (ANT-1) in a screen for dominant, apoptosis-inducing genes. ANT-1 is a component of the mitochondrial permeability transition complex, a protein aggregate connecting the inner with the outer mitochondrial membrane that has recently been implicated in apoptosis. ANT-1 expression led to all features of apoptosis, such as phenotypic alterations, collapse of the mitochondrial membrane potential, cytochrome c release, caspase activation, and DNA degradation. Both point mutations that impair ANT-1 in its known activity to transport ADP and ATP as well as the NH2-terminal half of the protein could still induce apoptosis. Interestingly, ANT-2, a highly homologous protein could not lead to cell death, demonstrating the specificity of the signal for apoptosis induction. In contrast to Bax, a proapoptotic Bcl-2 gene, ANT-1 was unable to elicit a form of cell death in yeast. This and the observed repression of apoptosis by the ANT-1–interacting protein cyclophilin D suggest that the suicidal effect of ANT-1 is mediated by specific protein–protein interactions within the permeability transition pore.