Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release
Bid-cardiolipin interaction at mitochondrial contact site contributes to mitochondrial cristae reorganization and cytochrome c release
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DOI：
10.1091/mbc.e03-12-0864
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发表时间：
2004-07-01
影响因子：
3.3
通讯作者：
Yin, XM
中科院分区：
文献类型：
--
作者：
Kim, TH;Zhao, Y;Yin, XM
细胞色素c从线粒体膜间隙的释放是由各种死亡刺激诱导的细胞凋亡的关键。Bid是一种仅含BH 3的促死亡Bcl-2家族蛋白，可以有效激活这种外排。在目前的研究中，我们调查了线粒体定位的投标及其相互作用与线粒体磷脂，重点是它们的关系，投标诱导细胞色素c的释放。我们发现Bid与线粒体的结合只需要其八个螺旋结构中的三个（α 4-α 6），而不需要BH 3结构域，并且这种结合不能被抗死亡分子Bcl-x（L）抑制。膜分离表明，TBID绑定到线粒体外膜在接触和非接触网站。Bid可以与完整线粒体上的特定心磷脂物质相互作用，如质谱法所鉴定。与与线粒体的结合一样，这种相互作用不能被BH 3结构域中的突变或Bcl-x（L）阻断。然而，心磷脂特异性染料，10-N-壬基吖啶橙子，可以优先抑制投标结合到线粒体接触点，抑制投标诱导的线粒体嵴重组和细胞色素c的释放。因此，这些研究结果表明，出价与线粒体心磷脂在接触网站的相互作用，可以显着地促进其功能。
Release of cytochrome c from the mitochondrial intermembrane space is critical to apoptosis induced by a variety of death stimuli. Bid is a BH3-only prodeath Bcl-2 family protein that can potently activate this efflux. In the current study, we investigated the mitochondrial localization of Bid and its interactions with mitochondrial phospholipids, focusing on their relationships with Bid-induced cytochrome c release. We found that Bid binding to the mitochondria required only three of its eight helical structures (alpha4-alpha6), but not the BH3 domain, and the binding could not be inhibited by the antideath molecule Bcl-x(L). Membrane fractionations indicated that tBid bound to mitochondrial outer membranes at both contact and noncontact sites. Bid could interact with specific cardiolipin species on intact mitochondria as identified by mass spectrometry. Like the binding to the mitochondria, this interaction could not be blocked by the mutation in the BH3 domain or by Bcl-x(L). However, a cardiolipin-specific dye, 10-N-nonyl acridine orange, could preferentially suppress Bid binding to the mitochondrial contact site and inhibit Bid-induced mitochondrial cristae reorganization and cytochrome c release. These findings thus suggest that interactions of Bid with mitochondrial cardiolipin at the contact site can contribute significantly to its functions.