ArticleThe EMBO journal2024
Glutamine sensing licenses cholesterol synthesis.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Endothelial SLC25A13 links glutamine metabolism to angiogenesis.EMBO molecular medicine · 2026Article
- A novel risk model of cholesterol metabolism-related mRNAs for predicting overall survival and immune signature in glioma based on machine learning and multi-omics data.Translational cancer research · 2026Article
- Effects of a Low-Fat Diet Supplemented with Plant Extract on Lipid Metabolism, Antioxidant Capacity, Inflammation, and Gut Microbiota in Healthy Beagles.Veterinary sciences · 2026Article
- Redirecting Cholesterol Metabolism DuringInternational journal of biological sciences · 2026Article
- Drug repurposing screen identifies an HRI activating compound that promotes adaptive mitochondrial remodeling in MFN2-deficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Rational Design of Non-Toxic Multidrug Combinations Demonstrates Durable and Hypoxia-Enhanced Efficacy Against Renal Cell Carcinoma.Pharmaceutics · 2025Article
- Article
- Drug Repurposing Screen Identifies an HRI Activating Compound that Promotes Adaptive Mitochondrial Remodeling in MFN2-deficient Cells.bioRxiv : the preprint server for biology · 2025Article
- Mitofusin 2 displays fusion-independent roles in proteostasis surveillance.Nature communications · 2025Article
- Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity.Nature metabolism · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
The mevalonate pathway produces essential lipid metabolites such as cholesterol. Although this pathway is negatively regulated by metabolic intermediates, little is known of the metabolites that positively regulate its activity. We found that the amino acid glutamine is required to activate the mevalonate pathway. Glutamine starvation inhibited cholesterol synthesis and blocked transcription of the mevalonate pathway-even in the presence of glutamine derivatives such as ammonia and α-ketoglutarate. We pinpointed this glutamine-dependent effect to a loss in the ER-to-Golgi trafficking of SCAP that licenses the activation of SREBP2, the major transcriptional regulator of cholesterol synthesis. Both enforced Golgi-to-ER retro-translocation and the expression of a nuclear SREBP2 rescued mevalonate pathway activity during glutamine starvation. In a cell model of impaired mitochondrial respiration in which glutamine uptake is enhanced, SREBP2 activation and cellular cholesterol were increased. Thus, the mevalonate pathway senses and is activated by glutamine at a previously uncharacterized step, and the modulation of glutamine synthesis may be a strategy to regulate cholesterol levels in pathophysiological conditions.
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Registered trials
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