Mitochondrial DNA damage and the aging process–facts and imaginations

Abstract

Mitochondrial DNA (mtDNA) is a circular double-stranded molecule organized in nucleoids and covered by the histone-like protein mitochondrial transcription factor A (TFAM). Even though mtDNA repair capacity appears to be adequate the accumulation of mtDNA mutations has been shown to be at least one important molecular mechanism of human aging. Reactive oxygen species (ROS), which are generated at the FMN moiety of mitochondrial respiratory chain (RC) complex I, should be considered to be important at least for the generation of age-dependent mtDNA deletions. However, the accumulation of acquired mutations to functionally relevant levels in aged tissues seems to be a consequence of clonal expansions of single founder molecules and not of ongoing mutational events.

• Mitochondrial DNA
• TFAM
• mtDNA
• FMN moiety

Notes

^*This article is dedicated to Prof. Dr Wolfgang Kunz (*6.5.1925–5.6.2006) who made important contributions to biochemical studies of isolated mitochondria, in particular by identifying the role of adenine nucleotide translocase for flux control of mitochondrial respiration.

^† Tel: [phone]. Fax: [phone]. [email protected].