Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin.

ABSTRACT: IDH1^R132H (isocitrate dehydrogenase 1) mutations play a key role in the development of low-grade gliomas. IDH1^wt converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP⁺), whereas IDH1^R132H uses α-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). While the effects of 2-HG have been the subject of intense research, the 2-HG independent effects of IDH1^R132H are still ambiguous. The present study demonstrates that IDH1^R132H expression but not 2-HG alone leads to significantly decreased tricarboxylic acid (TCA) cycle metabolites, reduced proliferation, and enhanced sensitivity to irradiation in both glioblastoma cells and astrocytes in vitro. Gliobla

SUBMITTER: Biedermann J 

PROVIDER: S-EPMC6966450 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature