Shimizu S, Tsujimoto Y
Osaka University Graduate School of Medicine, Biomedical Research Center, Department of Medical Genetics, CREST of Japan Science and Technology Corporation (JST), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):577-82. doi: 10.1073/pnas.97.2.577.
Through direct interaction with the voltage-dependent anion channel (VDAC), proapoptotic Bcl-2 family members such as Bax and Bak induce apoptogenic mitochondrial cytochrome c release and membrane potential (Deltapsi) loss in isolated mitochondria. Using isolated mitochondria, we showed that Bid and Bik, BH3-only proteins from the Bcl-2 family, induced cytochrome c release but not Deltapsi loss. Unlike Bax/Bak, the cytochrome c release induced by Bid/Bik was Ca(2+)-independent, cyclosporin A-insensitive, and respiration-independent. Furthermore, in contrast to Bax/Bak, Bid/Bik neither interacted with VDAC nor directly affected the VDAC activity in liposomes. Consistently, Bid/Bik induced apoptosis without Deltapsi loss, whereas Bax induced apoptosis with Deltapsi loss. These findings indicated the involvement of a different mechanism in BH3-only, protein-induced apoptogenic cytochrome c release.
通过与电压依赖性阴离子通道（VDAC）直接相互作用，促凋亡的Bcl-2家族成员（如Bax和Bak）可诱导分离的线粒体中凋亡相关的细胞色素c释放和膜电位（ΔΨ）丧失。利用分离的线粒体，我们发现Bid和Bik（Bcl-2家族中仅含BH3结构域的蛋白）可诱导细胞色素c释放，但不会导致膜电位丧失。与Bax/Bak不同，Bid/Bik诱导的细胞色素c释放不依赖于Ca(2+)，对环孢菌素A不敏感，且与呼吸无关。此外，与Bax/Bak相反，Bid/Bik既不与VDAC相互作用，也不直接影响脂质体中的VDAC活性。一致的是，Bid/Bik诱导凋亡时不会导致膜电位丧失，而Bax诱导凋亡时会导致膜电位丧失。这些发现表明，仅含BH3结构域的蛋白诱导凋亡相关细胞色素c释放涉及不同的机制。
