TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax
TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax
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DOI：
10.1038/sj.cdd.4402055
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发表时间：
2007-04-01
影响因子：
12.4
通讯作者：
Vallette, F. M.
中科院分区：
文献类型：
--
作者：
Bellot, G.;Cartron, P. -F.;Vallette, F. M.
Bax与线粒体的结合是细胞凋亡的重要步骤。通过使用细菌双杂交试验和交联策略，我们已经确定了TOM22，外线粒体膜（TOM）的易位酶的一个组成部分，作为Bax的线粒体受体。肽图显示Bax与TOM 22的相互作用涉及Bax的第一个α螺旋和可能的两个中心α螺旋，这与一些毒素的孔形成结构域同源。针对TOM22的抗体或TOM22表达的反义敲低特异性地抑制Bax与线粒体的结合，并防止Bax依赖性细胞凋亡。在酵母中，TOM22的单倍体菌株表现出TOM22的表达降低和异位表达的人Bax的线粒体缔合。我们的数据提供了一个新的视角与线粒体的Bax协会的机制，因为它涉及一个经典的进口途径。
The association of Bax with mitochondria is an essential step in the implementation of apoptosis. By using a bacterial two-hybrid assay and crosslinking strategies, we have identified TOM22, a component of the translocase of the outer mitochondrial membrane (TOM), as a mitochondrial receptor of Bax. Peptide mapping showed that the interaction of Bax with TOM22 involved the first alpha helix of Bax and possibly two central alpha helices, which are homologous to the pore forming domains of some toxins. Antibodies directed against TOM22 or an antisense knockdown of the expression of TOM22 specifically inhibited the association of Bax with mitochondria and prevented Bax-dependent apoptosis. In yeast, a haploid strain for TOM22 exhibited a decreased expression of TOM22 and mitochondrial association of ectopically expressed human Bax. Our data provide a new perspective on the mechanism of association of Bax with mitochondria as it involves a classical import pathway.