HtrA2 interacts with A beta peptide but does not directly alter its production or degradation

Mol Cells. 2005 Aug 31;20(1):83-9.

Abstract

HtrA2/Omi is a mammalian mitochondrial serine protease homologous to the E. coli HtrA/DegP gene products. Recently, HtrA2/Omi was found to have a dual role in mammalian cells, acting as an apoptosis-inducing protein and being involved in maintenance of mitochondrial homeostasis. By screening a human brain cDNA library with A beta peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of A beta peptide. The interaction between A beta peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in A beta peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of A beta peptide at the beta/gamma-secretase level, or the degradation of A beta peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of A beta40 and A beta42 by up to 30%. These results rule out the involvement of HtrA2/Omi in the etiology of Alzheimer's disease. However, the fact that overexpression of HtrA2/Omi reduces the generation of A beta40 and A beta42 suggests that it may play some positive role in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Apoptosis
  • Aspartic Acid Endopeptidases
  • Brain / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endopeptidases / metabolism
  • Gene Library
  • High-Temperature Requirement A Serine Peptidase 2
  • Humans
  • Mitochondrial Proteins
  • Serine Endopeptidases / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Amyloid beta-Peptides
  • Mitochondrial Proteins
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Serine Endopeptidases
  • HTRA2 protein, human
  • High-Temperature Requirement A Serine Peptidase 2
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human