Shi Yong, Chen Jianjun, Weng Changjiang, Chen Rui, Zheng Yanhua, Chen Quan, Tang Hong
The Center for Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
Biochem Biophys Res Commun. 2003 Jun 13;305(4):989-96. doi: 10.1016/s0006-291x(03)00871-4.
Bcl-2 family of proteins plays differential roles in regulation of mitochondria-mediated apoptosis, by either promoting or inhibiting the release of apoptogenic molecules from mitochondria to cytosol. Bcl-2 family proteins modulate the mitochondrial permeability through interaction with adenine nucleotide translocator (ANT), voltage-dependent anion channel (VDAC), ADP/ATP exchange, or oxidative phosphorylation during apoptosis. Although the mitochondrial homeostasis is affected by the relative ratio of pro- and anti-apoptotic Bcl-2 family members, the molecular mechanism underlying the release of mitochondrial intermembrane proteins remains elusive. Here we reported the biochemical evidence that both pro-apoptotic Bax and anti-apoptotic Bcl-X(L) might simultaneously contact the putative loop regions of human VDAC1, and the existence of VDAC1-Bax-Bcl-X(L) tertiary complex in vitro suggested that VDAC1 channel conformation and mitochondrial permeability could be determined by the delicate balance between Bax and Bcl-X(L).
Bcl-2蛋白家族在调节线粒体介导的细胞凋亡中发挥不同作用，通过促进或抑制凋亡分子从线粒体释放到细胞质中。在细胞凋亡过程中，Bcl-2家族蛋白通过与腺嘌呤核苷酸转位酶（ANT）、电压依赖性阴离子通道（VDAC）相互作用、ADP/ATP交换或氧化磷酸化来调节线粒体通透性。尽管线粒体稳态受促凋亡和抗凋亡Bcl-2家族成员的相对比例影响，但线粒体膜间蛋白释放的分子机制仍不清楚。在此，我们报告了生化证据，即促凋亡的Bax和抗凋亡的Bcl-X(L)可能同时接触人VDAC1的假定环区域，并且体外存在VDAC1-Bax-Bcl-X(L)三元复合物表明，VDAC1通道构象和线粒体通透性可能由Bax和Bcl-X(L)之间的微妙平衡决定。
