The mitochondrial serine protease HtrA2/Omi: an overview

Cell Death Differ. 2008 Mar;15(3):453-60. doi: 10.1038/sj.cdd.4402291. Epub 2008 Jan 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • High-Temperature Requirement A Serine Peptidase 2
  • Humans
  • Mice
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology*
  • Molecular Chaperones / chemistry
  • Molecular Sequence Data
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / genetics
  • Phylogeny
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*


  • Mitochondrial Proteins
  • Molecular Chaperones
  • Serine Endopeptidases
  • HTRA2 protein, human
  • High-Temperature Requirement A Serine Peptidase 2
  • Htra2 protein, mouse