Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane
Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane
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DOI：
10.1016/s0092-8674(02)01036-x
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发表时间：
2002-11-01
期刊：
影响因子：
64.5
通讯作者：
Newmeyer, DD
中科院分区：
文献类型：
--
作者：
Kuwana, T;Mackey, MR;Newmeyer, DD
Bcl-2家族蛋白调节细胞凋亡过程中线粒体中细胞色素c等蛋白质的释放。我们使用无细胞系统，并最终从定义的分子的囊泡重建表明，外膜透化Bcl-2家族蛋白质既不需要线粒体基质，内膜，也不需要其他蛋白质。Bid或其BH 3结构域肽激活单体Bax以产生允许非常大（2兆道尔顿）的葡聚糖分子通过的膜开口，解释了凋亡期间大线粒体蛋白的易位。这一过程需要心磷脂，并被抗凋亡Bcl-x（L）抑制。我们的结论是，线粒体蛋白质的释放在细胞凋亡中可以介导的超分子开放的线粒体外膜，促进BH 3/Bax/脂质相互作用和直接抑制Bcl-x（L）。
Bcl-2 family proteins regulate the release of proteins like cytochrome c from mitochondria during apoptosis. We used cell-free systems and ultimately a vesicular reconstitution from defined molecules to show that outer membrane permeabilization by Bcl-2 family proteins requires neither the mitochondrial matrix, the inner membrane, nor other proteins. Bid, or its BH3-domain peptide, activated monomeric Bax to produce membrane openings that allowed the passage of very large (2 megadalton) dextran molecules, explaining the translocation of large mitochondrial proteins during apoptosis. This process required cardiolipin and was inhibited by antiapoptotic Bcl-x(L). We conclude that mitochondrial protein release in apoptosis can be mediated by supramolecular openings in the outer mitochondrial membrane, promoted by BH3/Bax/lipid interaction and directly inhibited by Bcl-x(L).