System x c− (Sx c −) is a heteromeric antiporter (L-cystine/L-glutamate exchanger) expressed predominately on astrocytes in the central nervous system. Its activity contributes importantly to the maintenance of the ambient extracellular glutamate levels, as well as, to cellular redox homeostasis. Since alterations in glutamate levels

Isocitrate dehydrogenase (IDH) has gained much attention due its frequent mutation in acute myeloid leukemia (AML) and glioblastomas. This enzyme is responsible for converting isocitrate into α-ketoglutarate (α-KG); when this gene is mutated it further converts α-KG into another metabolite, D-2-HG, that competes with α-KG. Production of D-2-HG causes diversion to a new metabolic pathway, as well as inhibits the activity of other enzymes in the cell. We have created flies that express the IDH mutant protein to investigate the other metabolic changes. One of these changes results in an embryo lethality. Additional model systems investigating larval and adult brains have shown glial cell inhibition. We hypothesize that harboring the IDH mutation will have a negative impact on the stable development of progeny. Note: This abstract was not presented at the meeting. Citation Format: Nicholas DiDuca, Sarah H. Roberts, Shane Sturtevant, Marla Tipping. Investigating the role of IDH in normal metabolic and cancer pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4368.

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