Assessment of the "common" 4.8-kb mitochondrial DNA deletion and identification of several closely related deletions in the dorsal root ganglion of aging and streptozotocin rats.

Abstract

The identification of several mitochondrial DNA (mtDNA) deletions and the accumulation of the "common" 4.8-kb mitochondrial DNA deletion (mtDNA(4834)) with aging and experimental streptozotocin-induced diabetes (STZ) were studied in the rat dorsal root ganglion (DRG). Twenty-one mtDNA deletions, including mtDNA(4834), were identified in rat L4-L6 DRG mtDNA of 15-month-old Spraque-Dawley rats with 13 months of STZ and age-matched controls. These deletions were flanked by breakpoints that ranged from 16-bp direct repeats to no direct repeats. The sciatic nerve contained undetectable levels of mtDNA deletions. Levels of mtDNA(4834) in rat DRG mtDNA significantly accumulated with age at a rate much higher than those reported in the brain, yet were not statistically different in STZ. Southern blot analysis demonstrated no significant accumulation of the total amount of mtDNA deletions in STZ over age-matched controls. The accumulation of mtDNA(4834) has not been studied in rat peripheral nerve tissue. Our identification of several mtDNA deletions with and without direct repeats at their breakpoint support the hypothesis that deletions can occur by both the slip-replication model and random recombination. Although there is a significant increase in accumulation of mtDNA(4834) associated with aging, the lack of significant accumulations of mtDNA deletions in STZ over age-matched controls indicates that this type of mtDNA damage is likely not a major alteration in STZ, although the changes could be confined to a small population of neurons that undergo apoptosis between 8 and 15 months.