Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation.
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.
van Loo
G
G
Flanders Interuniversity Institute for Biotechnology and Ghent University, Department of Molecular Biology, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
Schotte
P
P
van Gurp
M
M
Demol
H
H
Hoorelbeke
B
B
Gevaert
K
K
Rodriguez
I
I
Ruiz-Carrillo
A
A
Vandekerckhove
J
J
Declercq
W
W
Beyaert
R
R
Vandenabeele
P
P
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*
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