Mitochondrial DNA repair and aging.
The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis.
Mandavilli
Bhaskar S
BS
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
Santos
Janine H
JH
Van Houten
Bennett
B
D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans; D004260:DNA Repair; D004272:DNA, Mitochondrial; D004331:Drosophila melanogaster; D004579:Electron Transport; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009154:Mutation; D017382:Reactive Oxygen Species / Q000009:adverse effects; D012441:Saccharomyces cerevisiae
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species