<i>C. elegans</i> Cytoplasmic Isocitrate Dehydrogenase Neomorphic G98N and R133H Mutants Produce the Oncometabolite 2-Hydroxyglutarate.

ABSTRACT: Isocitrate dehydrogenase (IDH) catalyzes the conversion of NAD(P)⁺ and isocitrate to NAD(P)H and α-ketoglutarate (αKG). The cytoplasmic enzyme IDH1 is important for producing NADPH for biosynthesis and for protecting against oxidative stress. IDH1 mutants, such as R132H found in glioblastomas and other types of human cancers, have a neomorphic activity that uses NADPH to reduce αKG to 2-hydroxyglutarate (2HG). 2HG interferes with the activity of important enzymes such as histone demethylases and TET demethylases. We hypothesized that Caenorhabditis elegans could be a good model system for studying oncogenic properties of mutant IDH1. To test this, we purified C. elegans cytoplasmic IDH-1 and two mutants, G98N and R133H, which correspond to human IDH1 mutants G97N a

SUBMITTER: Bouchard M 

PROVIDER: S-EPMC12427979 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature