ArticleNature chemical biology2022
Fumarate suppresses B-cell activation and function through direct inactivation of LYN.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- A guide to B cell metabolism.Nature reviews. Immunology · 2026Review
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Fumarate-induced succination of A-kinase anchor protein 12 exacerbates renal inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Integrated bioinformatics and machine learning for shared diagnostic genes and mechanisms between periodontitis and psoriasis.Clinical rheumatology · 2026Article
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Oncometabolite fumarate impairs ATR-CHK1 signaling by succinating RPA1 in fumarate hydratase-deficient renal cell carcinoma cells.Cancer & metabolism · 2026Article
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- Fumarate and fumarate hydratase: an immunometabolite regulator of inflammation and diseases.Frontiers in immunology · 2026Review
- Engineering a Multifunctional Nanozyme Platform for Synergistic Melanoma Therapy: Integrating Enzyme Activity, Immune Activation, and Low-Temperature Photothermal Effects.Angewandte Chemie (International ed. in English) · 2025Article
- Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.Molecular cancer · 2025Review
- Review
- Metabolic remodelling produces fumarate via the aspartate-argininosuccinate shunt in macrophages as an antiviral defence.Nature microbiology · 2025Article
- The role of fatty acid metabolism on B cells and B cell-related autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Metabolic determinants of germinal center B cell formation and responses.Nature chemical biology · 2025Article
- B cell immunometabolism in health and disease.Nature immunology · 2025Review
- Dimethyl fumarate promotes the degradation of HNF1B and suppresses the progression of clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Untargeted plasma metabolomics based on liquid chromatography-mass spectrometry for the analysis ofFrontiers in veterinary science · 2025Article
- Fumarate Hydratase Restrains mtDNA Attenuates LPS-Induced Acute Lung Injury Through cGAS-STING Pathways.Journal of inflammation research · 2025Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated B cells increase central carbon metabolism to fulfill their bioenergetic demands, yet the mechanistic basis for this, as well as metabolic regulation in B cells, remains largely unknown. Here, we demonstrate that B-cell activation reprograms the tricarboxylic acid cycle and boosts the expression of fumarate hydratase (FH), leading to decreased cellular fumarate abundance. Fumarate accumulation by FH inhibition or dimethyl-fumarate treatment suppresses B-cell activation, proliferation and antibody production. Mechanistically, fumarate is a covalent inhibitor of tyrosine kinase LYN, a key component of the BCR signaling pathway. Fumarate can directly succinate LYN at C381 and abrogate LYN activity, resulting in a block to B-cell activation and function in vitro and in vivo. Therefore, our findings uncover a previously unappreciated metabolic regulation of B cells, and reveal LYN is a natural sensor of fumarate, connecting cellular metabolism to B-cell antigen receptor signaling.
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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.