Wang Xiaochen, Yang Chonglin, Chai Jijie, Shi Yigong, Xue Ding
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Science. 2002 Nov 22;298(5598):1587-92. doi: 10.1126/science.1076194.
Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to apoptotic signals. However, the mechanisms underlying this process have not been resolved. We report that inactivation of the Caenorhabditis elegans AIF homolog wah-1 by RNA interference delayed the normal progression of apoptosis and caused a defect in apoptotic DNA degradation. WAH-1 localized in C. elegans mitochondria and was released into the cytosol and nucleus by the BH3-domain protein EGL-1 in a caspase (CED-3)-dependent manner. In addition, WAH-1 associated and cooperated with the mitochondrial endonuclease CPS-6/endonuclease G (EndoG) to promote DNA degradation and apoptosis. Thus, AIF and EndoG define a single, mitochondria-initiated apoptotic DNA degradation pathway that is conserved between C. elegans and mammals.
凋亡诱导因子（AIF）是一种线粒体氧化还原酶，在凋亡信号作用下会释放到细胞质中以诱导细胞死亡。然而，这一过程背后的机制尚未得到解决。我们报告称，通过RNA干扰使秀丽隐杆线虫AIF同源物wah-1失活会延迟凋亡的正常进程，并导致凋亡性DNA降解缺陷。WAH-1定位于秀丽隐杆线虫的线粒体中，并通过BH3结构域蛋白EGL-1以半胱天冬酶（CED-3）依赖的方式释放到细胞质和细胞核中。此外，WAH-1与线粒体核酸内切酶CPS-6/核酸内切酶G（EndoG）相互作用并协同作用，以促进DNA降解和凋亡。因此，AIF和EndoG定义了一条单一的、由线粒体启动的凋亡性DNA降解途径，该途径在秀丽隐杆线虫和哺乳动物之间是保守的。
