Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans.

Xiaochen Wang, Chonglin Yang, Jijie Chai, Yigong Shi, Ding Xue

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.

Science (New York, N.Y.) 2002 Nov 22

filter terms:

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.

Citation

Xiaochen Wang, Chonglin Yang, Jijie Chai, Yigong Shi, Ding Xue. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science (New York, N.Y.). 2002 Nov 22;298(5598):1587-92