title: Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation.
abstract: A hallmark of apoptosis is the fragmentation of nuclear DNA. Although this activity involves the caspase-3-dependent DNAse CAD (caspase-activated DNAse), evidence exists that DNA fragmentation can occur independently of caspase activity. Here we report on the ability of truncated Bid (tBid) to induce the release of a DNAse activity from mitochondria. This DNAse activity was identified by mass spectrometry as endonuclease G, an abundant 30 kDa protein released from mitochondria under apoptotic conditions. No tBid-induced endonuclease G release could be observed in mitochondria from Bcl-2-transgenic mice. The in vivo occurrence of endonuclease G release from mitochondria during apoptosis was confirmed in the liver from mice injected with agonistic anti-Fas antibody and is completely prevented in Bcl-2 transgenic mice. These data indicate that endonuclease G may be involved in CAD-independent DNA fragmentation during cell death pathways in which truncated Bid is generated.
authors.affiliation: Flanders Interuniversity Institute for Biotechnology and Ghent University, Department of Molecular Biology, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: van Loo
authors.forename: P
authors.initials: P
authors.lastname: Schotte
authors.forename: M
authors.initials: M
authors.lastname: van Gurp
authors.forename: H
authors.initials: H
authors.lastname: Demol
authors.forename: B
authors.initials: B
authors.lastname: Hoorelbeke
authors.forename: K
authors.initials: K
authors.lastname: Gevaert
authors.forename: I
authors.initials: I
authors.lastname: Rodriguez
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Carrillo
authors.forename: J
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: W
authors.initials: W
authors.lastname: Declercq
authors.forename: R
authors.initials: R
authors.lastname: Beyaert
authors.forename: P
authors.initials: P
authors.lastname: Vandenabeele
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation; D004706:Endodeoxyribonucleases / Q000378:metabolism / Q000502:physiology*; D019254:Genes, bcl-2 / Q000502:physiology; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D002352:Carrier Proteins; D003574:Cytochrome c Group; D024101:Mitochondrial Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases