Li H, Zhu H, Xu C J, Yuan J
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell. 1998 Aug 21;94(4):491-501. doi: 10.1016/s0092-8674(00)81590-1.
We report here that BID, a BH3 domain-containing proapoptotic Bcl2 family member, is a specific proximal substrate of Casp8 in the Fas apoptotic signaling pathway. While full-length BID is localized in cytosol, truncated BID (tBID) translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. tBID induces first the clustering of mitochondria around the nuclei and release of cytochrome c independent of caspase activity, and then the loss of mitochondrial membrane potential, cell shrinkage, and nuclear condensation in a caspase-dependent fashion. Coexpression of BclxL inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8.
我们在此报告，BID是含BH3结构域的促凋亡Bcl2家族成员，是Fas凋亡信号通路中Casp8的特异性近端底物。全长BID定位于细胞质中，而截短的BID（tBID）转位至线粒体，从而将凋亡信号从细胞质膜传导至线粒体。tBID首先诱导线粒体围绕细胞核聚集并独立于半胱天冬酶活性释放细胞色素c，然后以半胱天冬酶依赖的方式导致线粒体膜电位丧失、细胞皱缩和核浓缩。BclxL的共表达抑制了tBID诱导的所有凋亡变化。我们的结果表明，BID是Casp8诱导的线粒体损伤的介质。
