Bax 通道形成的动力学：离子强度的影响。
The dynamics of Bax channel formation: influence of ionic strength.
机构信息
University of Maryland, College Park, Maryland.
University of Maryland, College Park, Maryland.
出版信息
Biophys J. 2012 Aug 8;103(3):483-491. doi: 10.1016/j.bpj.2012.06.047.
Mitochondrial outer membrane permeabilization (MOMP) is a complex multistep process. Studies of MOMP in vivo are limited by the stochastic variability of MOMP between cells and rapid completion of IMS protein release within single cells. In vitro models have provided useful insights into MOMP. We have investigated the dynamics of Bax-mediated MOMP in isolated mitochondria using ionic strength as a tool to control the rate of MOMP. We find that Bax can induce both transient permeabilization, detected by protein release, and more substantial long-lasting permeabilization, measured by the rate of oxidation of added cytochrome c. We found that higher ionic strength causes Bax to form small channels quickly but the expansion of these early channels is impeded. This inhibitory effect of ionic strength is independent of tBid. Channels formed under low ionic strength are not destabilized by raising the ionic strength. Increase in ionic strength also increases the ability of Bcl-xL to inhibit Bax-mediated MOMP. Ionic strength does not affect Bax insertion into mitochondria. Thus, ionic strength influences the assembly of Bax molecules already in membrane into channels. Ionic strength can be used as an effective biophysical tool to study Bax-mediated channel formation.
线粒体外膜通透性（MOMP）是一个复杂的多步骤过程。由于细胞间 MOMP 的随机性变化以及单个细胞内 IMS 蛋白释放的快速完成，体内对 MOMP 的研究受到限制。体外模型为 MOMP 提供了有用的见解。我们使用离子强度作为工具来控制 MOMP 的速率，研究了分离线粒体中 Bax 介导的 MOMP 的动力学。我们发现 Bax 可以诱导瞬时通透性，通过蛋白质释放来检测，以及更实质性的持久通透性，通过添加细胞色素 c 的氧化速率来测量。我们发现较高的离子强度会使 Bax 快速形成小通道，但这些早期通道的扩展受到阻碍。离子强度的这种抑制作用独立于 tBid。在低离子强度下形成的通道不会因提高离子强度而失稳。增加离子强度还会增加 Bcl-xL 抑制 Bax 介导的 MOMP 的能力。离子强度不会影响 Bax 插入线粒体。因此，离子强度会影响已经在膜中的 Bax 分子组装成通道。离子强度可以用作研究 Bax 介导的通道形成的有效生物物理工具。
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