Stuck on an aging mitochondria

The mitochondrial theory of aging suggests that DNA damage in the mitochondrial genome leads to dysfunction and production of reactive oxygen species implicated in the aging process. This DNA damage partly results from mutagenic base lesions in the form of 7,8-dihydro-8-oxoguanine (8-oxoG) and uracil. Cells normally utilize DNA glycosylases, such an 8-oxoguannine-DNA glycosylase (OGG1) and uracil-DNA glycosylase (UDG), in the first step of repairing such DNA damage. Aging produces high levels of 8-oxoG damage in mitochondrial DNA, but the levels and activity of OGG1 are higher in mitochondrial extracts from older rodents. In the September 1 PNAS, Bartosz Szczesny and colleagues at the University of Texas Medical Branch show that this apparent inconsistency is caused by a large fraction of OGG1 being caught in the mitochondrial membrane (PNAS, DOI:10.1073/pnas.1932854100, September 1, 2003).

Szczesny et al. analyzed OGG1 levels in the mitochondrial extracts of two different systems: 4- and 20-month-old mouse ...