ArticleJournal of cell science2020
BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages.
Article in Journal of cell science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Branched Chain Amino Acid Metabolism in Developmental Brain Injury: Putative Mechanisms and Therapeutic Potential.Developmental neuroscience · 2026Review
- Multiple roles of branched-chain amino acid metabolism in tumour progression.Journal of biomedical science · 2025Review
- Metabolic profiling in experimental guinea pig models of bacterial and allergic inflammation.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- BCAT1 is a NOTCH1 target and sustains the oncogenic function of NOTCH1.Haematologica · 2025Article
- Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Reveals That TAM2-Driven Genes Affect Immunotherapeutic Response and Prognosis in Pancreatic Cancer.International journal of molecular sciences · 2023Article
- Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction.Nature metabolism · 2023Review
- A Transcriptomic Regulatory Network among miRNAs, lncRNAs, circRNAs, and mRNAs Associated with L-leucine-induced Proliferation of Equine Satellite Cells.Animals : an open access journal from MDPI · 2023Article
- The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity.Immunometabolism (Cobham, Surrey) · 2023Review
- Crosstalk between arginine, glutamine, and the branched chain amino acid metabolism in the tumor microenvironment.Frontiers in oncology · 2023Review
- Rewired Metabolism of Amino Acids and Its Roles in Glioma Pathology.Metabolites · 2022Review
- NMR-Based Metabolomics Identify Metabolic Change in Spleen of Idiopathic Thrombocytopenic Purpura Patients.Metabolites · 2022Article
- Immunometabolic crosstalk during bacterial infection.Nature microbiology · 2022Review
- The BCAT1 CXXC Motif Provides Protection against ROS in Acute Myeloid Leukaemia Cells.Antioxidants (Basel, Switzerland) · 2022Article
- The role of itaconate in host defense and inflammation.The Journal of clinical investigation · 2022Review
- Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages.Frontiers in immunology · 2022Article
- Aberrant branched-chain amino acid catabolism in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- Pyruvate Supports RET-Dependent Mitochondrial ROS Production to ControlFrontiers in immunology · 2022Article
- The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
In response to environmental stimuli, macrophages change their nutrient consumption and undergo an early metabolic adaptation that progressively shapes their polarization state. During the transient, early phase of pro-inflammatory macrophage activation, an increase in tricarboxylic acid (TCA) cycle activity has been reported, but the relative contribution of branched-chain amino acid (BCAA) leucine remains to be determined. Here, we show that glucose but not glutamine is a major contributor of the increase in TCA cycle metabolites during early macrophage activation in humans. We then show that, although uptake of BCAAs is not altered, their transamination by BCAT1 is increased following 8 h lipopolysaccharide (LPS) stimulation. Of note, leucine is not metabolized to integrate into the TCA cycle in basal or stimulated human macrophages. Surprisingly, the pharmacological inhibition of BCAT1 reduced glucose-derived itaconate, α-ketoglutarate and 2-hydroxyglutarate levels without affecting succinate and citrate levels, indicating a partial inhibition of the TCA cycle. This indirect effect is associated with NRF2 (also known as NFE2L2) activation and anti-oxidant responses. These results suggest a moonlighting role of BCAT1 through redox-mediated control of mitochondrial function during early macrophage activation.
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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.