Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization
Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization
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DOI：
10.1126/science.1074721
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发表时间：
2002-08-23
期刊：
影响因子：
56.9
通讯作者：
Lazebnik, Y
中科院分区：
文献类型：
--
作者：
Lassus, P;Opitz-Araya, X;Lazebnik, Y
目前的一种观点认为，细胞毒性应激，如DNA损伤，通过调节线粒体的通透性来诱导细胞凋亡。线粒体隔离了几种蛋白质，如果释放出来，就会通过激活半胱氨酸酶来杀死这些蛋白质，半胱氨酸酶是一种分解细胞的蛋白酶。细胞因子以一种不同的方式激活caspase，通过组装直接激活caspase的受体复合体；在这种情况下，随后的线粒体通透性通过放大caspase活性来加速细胞分解。我们发现，细胞毒性应激导致caspase-2的激活，而caspase-2是线粒体通透性所必需的。因此，我们认为，细胞因子诱导和应激诱导的细胞凋亡通过概念上相似的途径发挥作用，其中线粒体是caspase活性的放大者，而不是caspase激活的起始者。
A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by regulating the permeability of mitochondria. Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. Cytokines activate caspases in a different way, by assembling receptor complexes that activate caspases directly; in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation.