MITOCHONDRIAL ELECTRON-TRANSPORT CHAIN ACTIVITIES AND DNA DELETIONS IN REGIONS OF THE RAT-BRAIN

Deletions in human mitochondrial DNA cause various mitochondrial myopa thies and increase markedly with age in highly oxidative tissues, but exhibit a differential distribution in the brain. In order to determin e whether a similar pattern occurs in rat brain the levels of a 4.8 kb deletion and electron transport complex activities were measured in t he striatum, hippocampus, cerebellum, and cerebral cortex of young adu lt and senescent male Wistar rats. Deletion-containing mtDNA was prese nt 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, c erebral cortex, and cerebellum, respectively, of 22-23 mo old rats. To assess the relationship between fractional occurrence of a deletion a nd oxidative phosphorylation capacity, the activities of mitochondrial respiratory chain complexes I, III, IV and V, the mitochondrial ATP-a se, 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 a ge and to a large extent mirror the pattern observed in the human brai n, they appear to have no effect on capacity for oxidative phosphoryla tion of distinct brain regions. Any reductions in capacity that may be present are likely to occur only at the level of individual cells.