Mechanisms of AIF-Mediated Apoptotic DNA Degradation in Caenorhabditis elegans
- 22 November 2002
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 298 (5598) , 1587-1592
- https://doi.org/10.1126/science.1076194
Abstract
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 theCaenorhabditis 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.Keywords
This publication has 29 references indexed in Scilit:
- Identification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase InteractionJournal of Biological Chemistry, 2002
- NADH Oxidase Activity of Mitochondrial Apoptosis-inducing FactorJournal of Biological Chemistry, 2001
- Dominant cell death induction by extramitochondrially targeted apoptosis‐inducing factorThe FASEB Journal, 2001
- Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP ProteinsCell, 2000
- Smac, a Mitochondrial Protein that Promotes Cytochrome c–Dependent Caspase Activation by Eliminating IAP InhibitionCell, 2000
- Translocation of C. elegans CED-4 to Nuclear Membranes During Programmed Cell DeathScience, 2000
- Cell Death in DevelopmentCell, 1999
- Computational Method to Predict Mitochondrially Imported Proteins and their Targeting SequencesEuropean Journal of Biochemistry, 1996
- Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome cPublished by Elsevier ,1996
- Mutations Affecting Programmed Cell Deaths in the Nematode Caenorhabditis elegans sScience, 1983