Quantitative Variation in m.3243A > G Mutation Produce Discrete Changes in Energy Metabolism.

ABSTRACT: Mitochondrial DNA (mtDNA) 3243A > G tRNALeu^(UUR) heteroplasmic mutation (m.3243A > G) exhibits clinically heterogeneous phenotypes. While the high mtDNA heteroplasmy exceeding a critical threshold causes mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome, the low mtDNA heteroplasmy causes maternally inherited diabetes with or without deafness (MIDD) syndrome. How quantitative differences in mtDNA heteroplasmy produces distinct pathological states has remained elusive. Here we show that despite striking similarities in the energy metabolic gene expression signature, the mitochondrial bioenergetics, biogenesis and fuel catabolic functions are distinct in cells harboring low or high levels of the m.3243 A > G mutation compared to wild type c

SUBMITTER: McMillan RP 

PROVIDER: S-EPMC6453956 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature