Deletions in human mitochondrial DNA cause various mitochondrial myopathies and increase
markedly with age in highly oxidative tissues, but exhibit a differential distribution
in the brain. In order to determine whether a similar pattern occurs in rat brain
the levels of a 4.8 kb deletion and electron transport complex activities were measured
in the striatum, hippocampus, cerebellum, and cerebral cortex of young adult and senescent
male Wistar rats. Deletion-containing mtDNA was present at relatively similar levels
(0.0003%) in all regions in 6 mo rats, but increased 25-, 7-, 3-, and 2-fold in the
striatum, hippocampus, cerebral cortex, and cerebellum, respectively, of 22-23 mo
old rats. To assess the relationship between fractional occurrence of a deletion and
oxidative phosphorylation capacity, the activities of mitochondrial respiratory chain
complexes I, III, IV and V, the mitochondrial ATP-ase, each of which contains subunits
encoded in mtDNA, were determined in homogenates. No age-related decrements in activity
were observed in any of the brain regions. Thus, while mtDNA deletions increase with
age and to a large extent mirror the pattern observed in the human brain, they appear
to have no effect on capacity for oxidative phosphorylation of distinct brain regions.
Any reductions in capacity that may be present are likely to occur only at the level
of individual cells.