IDH1 mutations induce organelle defects via dysregulated phospholipids.

ABSTRACT: Infiltrating gliomas are devastating and incurable tumors. Amongst all gliomas, those harboring a mutation in isocitrate dehydrogenase 1 mutation (IDH1^mut) acquire a different tumor biology and clinical manifestation from those that are IDH1^WT. Understanding the unique metabolic profile reprogrammed by IDH1 mutation has the potential to identify new molecular targets for glioma therapy. Herein, we uncover increased monounsaturated fatty acids (MUFA) and their phospholipids in endoplasmic reticulum (ER), generated by IDH1 mutation, that are responsible for Golgi and ER dilation. We demonstrate a direct link between the IDH1 mutation and this organelle morphology via D-2HG-induced stearyl-CoA desaturase (SCD) overexpression, the rate-limiting enzyme in MUFA biosynthesis

SUBMITTER: Lita A 

PROVIDER: S-EPMC7840755 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature