The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. |
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Authors: | G van Loo M van Gurp B Depuydt S M Srinivasula I Rodriguez E S Alnemri K Gevaert J Vandekerckhove W Declercq P Vandenabeele |
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Affiliation: | Flanders 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. |
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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. |
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