We already have mentioned that mutagenic lesions can only become a mutation if DNA repair systems fail to repair the damage. Mitochondria appear to possess a limited repertoire of DNA repair pathways, and therefore are incapable of repairing certain types of DNA damage. However, they are proficient in BER, which operates on oxidatively damaged mtDNA. Measurements of the age-related changes in the activity of BER enzymes were used to infer mechanisms of accumulation of mtDNA mutations in aging. The methods used to evaluate activity of these enzymes are described in great detail by Nyaga and Bohr (2002) and will not be discussed here.
Earlier we mentioned the lack of consensus regarding the age-related trend in mitochondrial content of DNA-repair enzymes, with some groups reporting an increase and others reporting a decrease. Both increase and decrease in the activity of DNA-repair enzymes in mitochondria appear to be consistent with increased oxidative stress and an increased number of oxidative mtDNA lesions with aging, phenomena on which a consensus does exist. Therefore, decreased expression of DNA repair enzymes is believed to result in a decreased ability of mitochondria to repair oxidative lesions, which leads to their accumulation. On the other hand, increased expression of DNA repair enzymes was interpreted to represent an adaptive response to increased oxidative stress. The magnitude of this response is believed to be insufficient to completely protect mtDNA when oxidative stress overwhelms antioxidant and DNA-repair systems, resulting in the net accumulation of oxidative DNA lesions. This ambiguity in interpretation somewhat reduces the value of measuring changes in mtDNA repair pathways as end-point assay in studies of aging. Despite this drawback, measurements of DNA repair enzyme activities remain an invaluable component of global evaluation of mtDNA-related parameters in aging.
Was this article helpful?
Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...