Mitochondrial DNA damage and the aging process: facts and imaginations.
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.
Wiesner
Rudolf J
RJ
Faculty of Medicine, Institute of Vegetative Physiology, University of Köln, Köln, Germany. rudolf.wiesner@uni-koeln.de
Zsurka
Gábor
G
Kunz
Wolfram S
WS
D000375:Aging / Q000502:physiology*; D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D017353:Gene Deletion; D006657:Histones / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology; D010085:Oxidative Phosphorylation; D017354:Point Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006657:Histones; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C499631:TFAM protein, human; D014157:Transcription Factors