 |
| Original Paper |
| The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity |
|
| G van Loo1, M van Gurp1, B Depuydt1, S M Srinivasula2, I Rodriguez3, E S Alnemri2, K Gevaert4, J Vandekerckhove4, W Declercq1 and P Vandenabeele1 |
|
1Flanders Interuniversity Institute for Biotechnology and Ghent University, Molecular Signalling and Cell Death Unit, Department of Molecular Biology, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium
2Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
3The Rockefeller University, Laboratory of Vertebrate Neurobiology, New York, USA
4Flanders Interuniversity Institute for Biotechnology and Ghent University, Department of Medical Protein Research, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium
|
Correspondence to: P Vandenabeele, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium. Tel.: 32-9-264-51-31; Fax: 32-9-264-53-48; E-mail: peter.vandenabeele@rug.ac.be | |
Edited by G Melino |
|
| Abstract |
| Proteome analysis of supernatant of isolated mitochondria exposed to recombinant tBid, a proapoptotic Bcl-2 member, revealed the presence of the serine protease Omi, also called HtrA2. This release was prevented in mitochondria derived from Bcl-2-transgenic mice. Release of Omi under apoptotic conditions was confirmed in vivo in livers from mice injected with agonistic anti-Fas antibodies and was prevented in livers from Bcl-2 transgenic mice. Omi release also occurs in apoptotic dying but not in necrotic dying fibrosarcoma L929 cells, treated with anti-Fas antibodies and TNF, respectively. The amino acid sequence reveals the presence of an XIAP interaction motif at the N-terminus of mature Omi. We demonstrate an interaction between endogeneous Omi and recombinant XIAP. Furthermore we show that endogenous Omi is involved in enhanced activation of caspases in cytosolic extracts. Cell Death and Differentiation (2002) 9, 20-26 DOI: 10.1038/sj/cdd/4400970 |
|
| Keywords |
| apoptosis; caspase; mitochondria; tBid; serine protease; Omi; HtrA2 |
|
| Abbreviations |
| BIR, Baculovirus IAP repeat; DIABLO, direct IAP binding protein with low pI; MALDI, matrix-assisted laser desorption ionization; MBP, maltose binding protein; MS, mass spectrometry; PSD, post-source decay; Smac, second mitochondria-derived activator of caspase; tBid, truncated Bid; XIAP, X-linked inhibitor of apoptosis protein |
|
|
|
|
| Received 12 October 2001; revised 18 October 2001; accepted 18 October 2001 |
|
| January 2002, Volume 9, Number 1, Pages 20-26 |
| Table of contents Previous Abstract Next Full text PDF |
|
