ArticleCancer research2018
2-Hydroxyglutarate-Mediated Autophagy of the Endoplasmic Reticulum Leads to an Unusual Downregulation of Phospholipid Biosynthesis in Mutant IDH1 Gliomas.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- Association of Autophagy-Related Gene Expression Profiles with Survival in Diffuse Astrocytic Tumors.Cancers · 2026Article
- MARCH6 Confers Protection Against Endoplasmic Reticulum Autophagy in Gliomas by Destabilizing FAM134B.Neurochemical research · 2026Article
- Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target.Research square · 2025Article
- The association of serum phospholipids levels with chronic liver diseases: A systematic review of observational studies.Health promotion perspectives · 2025Review
- Preparation and Preclinical Evaluation ofMolecules (Basel, Switzerland) · 2024Article
- The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches.Biochemical Society transactions · 2023Review
- PRMT1 driven PTX3 regulates ferritinophagy in glioma.Autophagy · 2023Article
- MiR-217 regulates autophagy through OPG/RANKL/RANK in giant cell tumors.Journal of orthopaedic surgery and research · 2023Article
- Role of endoplasmic reticulum autophagy in acute lung injury.Frontiers in immunology · 2023Review
- Preclinical modeling of lower-grade gliomas.Frontiers in oncology · 2023Review
- Lipid Alterations in Glioma: A Systematic Review.Metabolites · 2022Review
- Deuterium Metabolic Imaging Reports on TERT Expression and Early Response to Therapy in Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Deuterium magnetic resonance spectroscopy enables noninvasive metabolic imaging of tumor burden and response to therapy in low-grade gliomas.Neuro-oncology · 2022Article
- Article
- Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.Cancer imaging : the official publication of the International Cancer Imaging Society · 2022Article
- Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line.Nutrients · 2022Article
- Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations.Cell reports. Medicine · 2021Review
- Advances in ER-Phagy and Its Diseases Relevance.Cells · 2021Review
- Metabolic imaging detects elevated glucose flux through the pentose phosphate pathway associated with TERT expression in low-grade gliomas.Neuro-oncology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Tumor metabolism is reprogrammed to meet the demands of proliferating cancer cells. In particular, cancer cells upregulate synthesis of the membrane phospholipids phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdE) in order to allow for rapid membrane turnover. Nonetheless, we show here that, in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is downregulated and results in lower levels of both phospholipids when compared with wild-type IDH1 cells. 2-HG inhibited collagen-4-prolyl hydroxylase activity, leading to accumulation of misfolded procollagen-IV in the endoplasmic reticulum (ER) of both genetically engineered and patient-derived IDHmut glioma models. The resulting ER stress triggered increased expression of FAM134b, which mediated autophagic degradation of the ER (ER-phagy) and a reduction in the ER area. Because the ER is the site of phospholipid synthesis, ER-phagy led to reduced PtdCho and PtdE biosynthesis. Inhibition of ER-phagy via pharmacological or molecular approaches restored phospholipid biosynthesis in IDHmut glioma cells, triggered apoptotic cell death, inhibited tumor growth, and prolonged the survival of orthotopic IDHmut glioma-bearing mice, pointing to a potential therapeutic opportunity. Glioma patient biopsies also exhibited increased ER-phagy and downregulation of PtdCho and PtdE levels in IDHmut samples compared with wild-type, clinically validating our observations. Collectively, this study provides detailed and clinically relevant insights into the functional link between oncometabolite-driven ER-phagy and phospholipid biosynthesis in IDHmut gliomas.
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