Accelerated expansion of pathogenic mitochondrial DNA heteroplasmies in Huntington's disease.

ABSTRACT: Mitochondrial dysfunction is found in the brain and peripheral tissues of patients diagnosed with Huntington's disease (HD), an irreversible neurodegenerative disease of which aging is a major risk factor. Mitochondrial function is encoded by not only nuclear DNA but also DNA within mitochondria (mtDNA). Expansion of mtDNA heteroplasmies (coexistence of mutated and wild-type mtDNA) can contribute to age-related decline of mitochondrial function but has not been systematically investigated in HD. Here, by using a sensitive mtDNA-targeted sequencing method, we studied mtDNA heteroplasmies in lymphoblasts and longitudinal blood samples of HD patients. We found a significant increase in the fraction of mtDNA heteroplasmies with predicted pathogenicity in lymphoblasts from 1,549 HD patients rel

SUBMITTER: Wang Y 

PROVIDER: S-EPMC8325154 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature