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

Meng Lu Liu, Ming Jie Liu, Jin Man Kim, Hyeon Jin Kim, Jeong Hak Kim, Seong Tshool Hong

Research output: Contribution to journalArticle

15 Scopus citations

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 Aβ peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of Aβ peptide. The interaction between Aβ peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in Aβ peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of Aβ peptide at the β/γ- secretase level, or the degradation of Aβ peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of Aβ40 and Aβ42 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 Aβ40 and Aβ42 suggests that it may play some positive role in mammalian cells.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalMolecules and Cells
Volume20
Issue number1
StatePublished - Dec 1 2005

Keywords

  • Alzheimer's Disease
  • Apoptosis
  • Aβ Peptide
  • HtrA2/Omi
  • Mitochondria Homeostasis
  • Secretase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Liu, M. L., Liu, M. J., Kim, J. M., Kim, H. J., Kim, J. H., & Hong, S. T. (2005). HtrA2 interacts with Aβ peptide but does not directly alter its production or degradation. Molecules and Cells, 20(1), 83-89.