Given that our study has shown increased oxidative damage to leukocyte DNA in HD and mitochondrial DNA is highly vulnerable to oxidative stress [31], the increased 4977 bp-deleted mtDNA in HD leukocytes most likely is due to increased oxidative damage to mtDNA. Our finding in peripheral blood parallels increased mitochondrial DNA
ha peptide level in the temporal and frontal cortices of HD patients [15]. We have also demonstrated increased total mtDNA copy number in peripheral leukocytes, which may be a compensatory response to increased oxidative stress [32]. Although total mtDNA copy number was increased in HD leukocytes, transcription levels of mtDNA-encoded
enzymes were not significantly elevated in our study. The transcription level of mtDNA depends on mtDNA copy number, and more importantly on the quality of mtDNA, other transcription factors and stability and quality of mitochondrial mRNA [25]. It is plausible that the oxidative damage to mtDNA in HD leukocytes has reached the threshold over which mtDNA-encoded mRNA expression was suppressed.