Virtually every cancer studied so far shows elevated choline and ethanolamine phospholipid metabolism, which has emerged as a metabolic hallmark of cancer. Here, we show that, unusually, low-grade gliomas carrying a mutation in isocitrate dehydrogenase 1 (IDHmut) down-regulate phosphatidylcholine and phosphatidylethanolamine biosynthesis and steady-state levels. Mechanistically, this down-regulation is mediated via autophagic degradation of the endoplasmic reticulum, the site of phospholipid biosynthesis. Importantly, the autophagy inhibitor chloroquine restores phospholipid levels and abrogates IDHmut tumor growth, identifying a potential therapeutic opportunity. Thus, our study demonstrates that IDHmut gliomas uniquely down-regulate phospholipid biosynthesis and that this phenomenon can be exploited for therapy.