| First Author | Wang XL | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 482 |
| Issue | 4 | Pages | 928-934 |
| PubMed ID | 27894840 | Mgi Jnum | J:241682 |
| Mgi Id | MGI:5903367 | Doi | 10.1016/j.bbrc.2016.11.135 |
| Citation | Wang XL, et al. (2017) Overexpression of MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10. Biochem Biophys Res Commun 482(4):928-934 |
| abstractText | Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid (Abeta) peptide in the brain, which is produced by the proteolysis of beta-amyloid precursor protein (APP). Recently, the mitochondrial transcription factor 4 (MTERF4), a member of the MTERF family, was implicated in regulating mitochondrial DNA transcription and directly in controlling mitochondrial ribosomal translation. The present study identified a novel role for MTERF4 in shifting APP processing toward the amyloidogenic pathway. The levels of MTERF4 protein were significantly increased in the hippocampus of APP/PS1 mice. In addition, the overexpression of MTERF4 induced a significant increase in the levels of APP protein and secreted Abeta42 in HEK293-APPswe cells compared with control cells. Further, MTERF4 overexpression shifted APP processing from alpha-to beta-cleavage, as indicated by decreased C83 levels and elevated C99 levels. Finally, the MTERF4 overexpression suppressed a disintegrin and metalloproteinase 10 (ADAM10) expression via a transcriptional mechanism. Taken together, these results suggest that MTERF4 promotes the amyloidogenic processing of APP by inhibiting ADAM10 in HEK293-APPswe cells; therefore, MTERF4 may play an important role in the pathogenesis of AD. |
