Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells

FEBS J. 2009 Jul;276(14):3800-9. doi: 10.1111/j.1742-4658.2009.07094.x. Epub 2009 Jun 3.


There is strong evidence that beta-amyloid (Abeta) causes oxidative stress and induces mitochondrial dysfunction in the pathogenesis of Alzheimer's disease. Mitochondrial transcription factor A (Tfam) has multiple roles in the maintenance of mtDNA. To study the protective roles of Tfam against amyloid neurotoxicity, we established SH-SY5Y cell lines stably overexpressing Tfam and exposed them to 10 microm Abeta1-42 for 24 h. We found that Tfam overexpression attenuated Abeta1-42-induced cell viability damage and apoptosis. In addition, Tfam overexpression significantly suppressed the increase in excess reactive oxygen species and reversed the reduction in cytochrome c oxidase activity and ATP production induced by Abeta1-42. Furthermore, overexpression of DeltaC-Tfam, which has no functional domain for stimulating mtDNA transcription but can still maintain the mtDNA nucleoid formation and mtDNA copy number, also exhibited protective effects against Abeta1-42 cytotoxicity in SH-SY5Y cells. Together, our data suggest that Tfam overexpression protects mitochondria against Abeta-induced oxidative damage in SH-SY5Y cells. These beneficial effects may be attributable to the roles of Tfam in maintaining mtDNA nucleoid formation and mtDNA copy number.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Damage
  • DNA, Mitochondrial / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electron Transport Complex IV / metabolism
  • Gene Dosage
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Oxidative Stress*
  • Peptide Fragments / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Amyloid beta-Peptides
  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Peptide Fragments
  • TFAM protein, human
  • Transcription Factors
  • amyloid beta-protein (1-42)
  • Adenosine Triphosphate
  • Electron Transport Complex IV