Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans

被引：321

作者：

Wang, XC

Yang, CL

Chai, JJ

Shi, YG

Xue, D ^{[1
]}

机构：

[1] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA

[2] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

来源：

SCIENCE | 2002年 / 298卷 / 5598期

关键词：

D O I：

10.1126/science.1076194

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 de. ne a single, mitochondria-initiated apoptotic DNA degradation pathway that is conserved between C. elegans and mammals.

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页码：1587 / 1592

页数：6

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