1. ¹Department for Molecular Biomedical Research, Unit for Molecular Signalling and Cell Death, VIB, Ghent, Belgium
2. ²Department of Molecular Biology, Unit for Molecular Signalling and Cell Death, Ghent University, Ghent, Belgium

Correspondence: P Vandenabeele, Department for Molecular Biomedical Research, Unit for Molecular Signalling and Cell Death, VIB, Ghent University, Technologiepark 927, Zwijnaarde B-9052, Belgium. Tel: +32 9 3313763; Fax: +32 9 3313609; E-mail: peter.vandenabeele@dmbr.ugent.be

³Current address: Department of Physiological Chemistry, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Received 23 July 2007; Revised 17 October 2007; Accepted 18 October 2007; Published online 4 January 2008.

Abstract

The HtrA family refers to a group of related oligomeric serine proteases that combine a trypsin-like protease domain with at least one PDZ interaction domain. Mammals encode four HtrA proteases, named HtrA1–4. The protease activity of the HtrA member HtrA2/Omi is required for mitochondrial homeostasis in mice and humans and inactivating mutations associated with neurodegenerative disorders such as Parkinson's disease. Moreover, HtrA2/Omi is released in the cytosol, where it contributes to apoptosis through both caspase-dependent and -independent pathways. Here, we review the current knowledge of HtrA2/Omi biology and discuss the signaling pathways that underlie its mitochondrial and apoptotic functions from an evolutionary perspective.