Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans.
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.
Wang
Xiaochen
X
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Yang
Chonglin
C
Chai
Jijie
J
Shi
Yigong
Y
Xue
Ding
D
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D018509:DNA, Helminth / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005420:Flavoproteins / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016415:Sequence Alignment
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D029742:Caenorhabditis elegans Proteins; C469544:Cps-6 protein, C elegans; D018509:DNA, Helminth; C112486:EGL-1 protein, C elegans; D005420:Flavoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C469543:Wah-1 protein, C elegans; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases; C089223:ced-3 protein, C elegans