GSE129091 Quantitative variation in m.3243A > G mutation produce discrete changes in energy metabolism

Contributors : Ryan P McMillan ; Sidney Stewart ; James A Budnick ; Clayton C Caswell ; Matthew W Hulver ; Konark Mukherjee ; Sarika SrivastavaSeries Type : Expression profiling by arrayOrganism : Homo sapiensMitochondrial 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.3243A>G mutation compared to wild type cells. We further demonstrate that the low heteroplasmic mutant cells exhibit a coordinate induction of transcriptional regulators of the mitochondrial biogenesis, glucose and fatty acid metabolism pathways that lack in near homoplasmic mutant cells compared to wild type cells. Altogether, these results shed new biological insights on the potential mechanisms by which low mtDNA heteroplasmy may progressively cause diabetes mellitus.

Source: GEO: Gene Expression Omnibus - April 9, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research