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Science 22 November 2002:
Vol. 298. no. 5598, pp. 1587 - 1592
DOI: 10.1126/science.1076194
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Research Articles

Mechanisms of AIF-Mediated Apoptotic DNA Degradation in Caenorhabditis elegans

Xiaochen Wang,1* Chonglin Yang,1* Jijie Chai,2 Yigong Shi,2 Ding Xue1dagger

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.

1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
2 Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: ding.xue{at}colorado.edu

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