Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation
van Loo, G × Schotte, P van Gurp, M Demol, H Hoorelbeke, Bart Gevaert, K Rodriguez, I Ruiz-Carrillo, A Vandekerckhove, J Declercq, W Beyaert, R Vandenabeele, P #
Cell death and differentiation vol:8 issue:12 pages:1136-42
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.