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Overexpression of MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10

Xiao-Liang Wang1, Qing Liu1, Guo-Jun Chen2

  • 1Department of Clinical Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Biochemical and Biophysical Research Communications
|November 30, 2016
PubMed

Insights

Mitochondrial transcription factor 4 (MTERF4) promotes Alzheimer's disease pathology by increasing amyloid-beta production. MTERF4 shifts amyloid precursor protein processing towards the amyloidogenic pathway, potentially contributing to AD pathogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Alzheimer's disease (AD) is linked to β-amyloid (Aβ) peptide deposition in the brain.
  • Aβ is generated from the amyloid precursor protein (APP) through proteolytic processing.
  • Mitochondrial transcription factor 4 (MTERF4) is known for its role in mitochondrial gene expression.

Purpose of the Study:

  • To investigate the novel role of MTERF4 in the processing of APP.
  • To determine if MTERF4 influences the amyloidogenic pathway in Alzheimer's disease.

Main Methods:

  • Quantified MTERF4 protein levels in the hippocampus of APP/PS1 mice.
  • Overexpressed MTERF4 in HEK293-APPswe cells to assess APP processing.
  • Measured levels of APP, secreted Aβ42, C83, and C99 peptides.
  • Assessed the effect of MTERF4 on ADAM10 expression.

Main Results:

  • MTERF4 protein levels were elevated in the hippocampus of APP/PS1 mice.
  • MTERF4 overexpression increased APP and secreted Aβ42 levels in HEK293-APPswe cells.
  • MTERF4 shifted APP processing from α-cleavage to β-cleavage, indicated by altered C83 and C99 levels.
  • MTERF4 suppressed ADAM10 expression transcriptionally.

Conclusions:

  • MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10.
  • MTERF4 may play a significant role in the pathogenesis of Alzheimer's disease.
Keywords:
ADAM10Alzheimer's diseaseAmyloid precursor proteinBACE1MTERF4

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