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

Abstract

There is strong evidence that β-amyloid (Aβ) 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 μm Aβ1-42 for 24 h. We found that Tfam overexpression attenuated Aβ1-42-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 Aβ1-42. Furthermore, overexpression of ΔC-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 Aβ1-42 cytotoxicity in SH-SY5Y cells. Together, our data suggest that Tfam overexpression protects mitochondria against Aβ-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. © 2009 FEBS.