Region-specific changes in mitochondrial D-loop in aged rat CNS.
Impaired mitochondrial oxidative phosphorylation (OXPHOS) is considered a cause of aging. A reduction in mitochondrial DNA (mtDNA) replication and/or transcription may contribute to this OXPHOS diminution. Impairments in the displacement (D) loop, or non-coding, region of the mitochondrial genome, or accumulation of mtDNA mutations, may affect mtDNA replication and transcription. We determined the effects of age on the D-loop and on mtDNA deletion mutations in the spinal cord, medulla, midbrain, cerebellum, striatum, and cerebral cortex of Fischer 344 rats. D-loop, 7S DNA levels were reduced by 3-fold in striatum, 2.5-fold in cortex, and 2-fold in the spinal cord of older animals. We did not detect a population of mtDNA affected by the most prevalent known (ND4-containing) deletions, indicating they do not comprise a significant portion of total mtDNA. However, we detected an age-related and region-specific increase in the common deletion, which comprised 0.0003-0.0007% of total mtDNA. Mitochondrial genome copy number varied between regions, in addition to an overall 18% decrease with age across the whole brain. These results suggest the age-related decline in OXPHOS may be related to a reduction in D-loop function.
Discipline of Anatomy, School of Biomedical Sciences, Faculty of Health and The Center for Brain and Mental Health Research, University of Newcastle, Callaghan, NSW 2308, Australia.
Simone C
SC
McInerny
Amanda L
AL
Brown
Doug W
DW
Smith
D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000235:genetics*; D018628:Gene Dosage; D008297:Male; D010085:Oxidative Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D017384:Sequence Deletion
D004272:DNA, Mitochondrial