Ho Andrew T, Zacksenhaus Eldad
Division of Cell & Molecular Biology, Toronto General Research Institute-University Health Network, Toronto, Ontario, Canada.
Cell Cycle. 2004 Apr;3(4):446-8. Epub 2004 Apr 1.
Assembly of the apoptosome in response to mitochondrial permeabilization, the hallmark of the intrinsic apoptotic pathway, involves binding of cytochrome c to Apaf1, recruitment and auto-processing of the apical/signaling pro-caspase-9, and coupled activation of downstream/executioner caspases like caspase 3. Evidence now indicates that certain apoptotic cascades can bypass the apoptosome and activate caspase-9 independent of the mitochondria. Recently, we have demonstrated that caspase-9 can be activated in Apaf1-mutant primary myoblasts, but not fibroblasts, in response to stimuli that are known to act via the mitochondria. Thus, apoptosomal activation of caspase-9 seems to represent only one of the routes for its activation; other pathways, some of which are yet to be discovered, can bypass the requirement for Apaf1 and activate caspase-9 in a tissue and context specific manner.
响应线粒体通透性改变（这是内源性凋亡途径的标志）而组装凋亡小体，涉及细胞色素c与凋亡蛋白酶激活因子-1（Apaf1）的结合、顶端/信号前体半胱天冬酶-9的募集和自身加工，以及下游/效应半胱天冬酶（如半胱天冬酶-3）的偶联激活。现在有证据表明，某些凋亡级联反应可以绕过凋亡小体，独立于线粒体激活半胱天冬酶-9。最近，我们已经证明，在已知通过线粒体起作用的刺激下，半胱天冬酶-9可以在Apaf1突变的原代成肌细胞中被激活，但在成纤维细胞中则不能。因此，半胱天冬酶-9的凋亡小体激活似乎只是其激活途径之一；其他途径，其中一些尚未被发现，可以绕过对Apaf1的需求，并以组织和背景特异性的方式激活半胱天冬酶-9。
