ArticleBiochimica et biophysica acta. Bioenergetics2019
Glutamine regulates mitochondrial uncoupling protein 2 to promote glutaminolysis in neuroblastoma cells.
Article in Biochimica et biophysica acta. Bioenergetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Pro- and Anti-Inflammatory Macrophages Adjust UCP2 Protein Levels Based on Their Intrinsic Metabolism and Available Metabolites.European journal of immunology · 2026Article
- Uncoupling protein 2 and signal transducer and activator of transcription 1 are targets of human papillomavirus oncoproteins and may be prognostic markers for cervical cancer development.Frontiers in oncology · 2025Article
- The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives.International journal of molecular sciences · 2024Review
- Glutaminolysis is associated with mitochondrial pathway activation and can be therapeutically targeted in glioblastoma.Cancer & metabolism · 2024Article
- Differential regulation of mitochondrial uncoupling protein 2 in cancer cells.Biochimica et biophysica acta. Bioenergetics · 2024Article
- The 2-oxoglutarate/malate carrier extends the family of mitochondrial carriers capable of fatty acid and 2,4-dinitrophenol-activated proton transport.Acta physiologica (Oxford, England) · 2024Article
- Mitochondrial metabolism regulation and epigenetics in hypoxia.Frontiers in physiology · 2024Review
- Monitoring and modelling the glutamine metabolic pathway: a review and future perspectives.Metabolomics : Official journal of the Metabolomic Society · 2023Review
- Role of UCP2 in the Energy Metabolism of the Cancer Cell Line A549.International journal of molecular sciences · 2023Article
- Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class.International journal of molecular sciences · 2023Article
- Role of Mitochondrial Transporters on Metabolic Rewiring of Pancreatic Adenocarcinoma: A Comprehensive Review.Cancers · 2023Review
- UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control.International journal of molecular sciences · 2022Review
- Brown adipocytes promote epithelial mesenchymal transition of neuroblastoma cells by inducing PPAR-γ/UCP2 expression.Adipocyte · 2022Article
- Lipotoxicity in a Vicious Cycle of Pancreatic Beta Cell Exhaustion.Biomedicines · 2022Article
- Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives.Cancers · 2022Review
- Uncoupling proteins in the mitochondrial defense against oxidative stress.Progress in retinal and eye research · 2021Review
- UCP2 as a Potential Biomarker for Adjunctive Metabolic Therapies in Tumor Management.Frontiers in oncology · 2021Review
- On the Origin of ATP Synthesis in Cancer.iScience · 2020Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial uncoupling protein 2 (UCP2) is highly abundant in rapidly proliferating cells that utilize aerobic glycolysis, such as stem cells, cancer cells, and cells of the immune system. However, the function of UCP2 has been a longstanding conundrum. Considering the strict regulation and unusually short life time of the protein, we propose that UCP2 acts as a "signaling protein" under nutrient shortage in cancer cells. We reveal that glutamine shortage induces the rapid and reversible downregulation of UCP2, decrease of the metabolic activity and proliferation of neuroblastoma cells, that are regulated by glutamine per se but not by glutamine metabolism. Our findings indicate a very rapid (within 1 h) metabolic adaptation that allows the cell to survive by either shifting its metabolism to the use of the alternative fuel glutamine or going into a reversible, more quiescent state. The results imply that UCP2 facilitates glutamine utilization as an energetic fuel source, thereby providing metabolic flexibility during glucose shortage. The targeting UCP2 by drugs to intervene with cancer cell metabolism may represent a new strategy for treatment of cancers resistant to other therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.