ArticleNature metabolism2022
Metabolon formation regulates branched-chain amino acid oxidation and homeostasis.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- BCAT2 links branched-chain amino acids metabolism to interferon signaling to sustain macrophage inflammation.Nature immunology · 2026Article
- Perirenal fat β₃-adrenergic signaling alleviates renal fibrosis via regulating Bcat2/BCAA-TNFα pathway in diabetic kidney disease.Nature communications · 2026Article
- Exercise suppresses IP6K3 to modulate BCAA metabolism and ferroptosis in MASLD.Cellular & molecular biology letters · 2026Article
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- Highly dynamic assemblies of glycolytic enzymes by quinary determinants.Nature communications · 2026Article
- MTFR2 promotes VDAC1 oligomerization to reprogram BCAA metabolism in tumor cells to polarize TAMs in LUAD.Cell death & disease · 2026Article
- Blood Focused-Metabolomics and Transcriptomics Uncover Non-Linear Risk Association of Inadequate Dietary Choline Intake-Linked Metabolic Stress with MASLD Through Amino Acid Biomarkers,International journal of molecular sciences · 2026Article
- Article
- Multimodal Therapeutic Strategies Targeting BCAA Metabolism in Diabetic Cardiomyopathy: A Path to Cardioprotection.Cardiovascular toxicology · 2025Review
- A mouse model for hemoglobin SC disease recapitulates characteristic human pathologies.Blood advances · 2025Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Cancer-Type-Specific DNA Methylation Is a Source of Vulnerability in Liver Cancer Cells.Cancer science · 2025Article
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
- Gut Microbiota Dysbiosis and Its Impact on Type 2 Diabetes: From Pathogenesis to Therapeutic Strategies.Metabolites · 2025Review
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- BCAT1 Activation Reprograms Branched-Chain Amino Acid Metabolism and Epigenetically Promotes Inflammation in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2025Article
- Branched-chain amino acid transferase type 2 (BCAT2) deficiency: Report of an eighth case and literature review.Molecular genetics and metabolism reports · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Branched-chain amino acids and insulin resistance in type 2 diabetes: from metabolic dysregulation to therapeutic targets.Frontiers in endocrinology · 2025Review
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15 authors at 3 institutions in 1 country.
Funding
Abstract
The branched-chain aminotransferase isozymes BCAT1 and BCAT2, segregated into distinct subcellular compartments and tissues, initiate the catabolism of branched-chain amino acids (BCAAs). However, whether and how BCAT isozymes cooperate with downstream enzymes to control BCAA homeostasis in an intact organism remains largely unknown. Here, we analyse system-wide metabolomic changes in BCAT1- and BCAT2-deficient mouse models. Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain α-keto acids (BCKAs), causing morbidity and mortality that can be ameliorated by dietary BCAA restriction. Through proximity labelling, isotope tracing and enzymatic assays, we provide evidence for the formation of a mitochondrial BCAA metabolon involving BCAT2 and branched-chain α-keto acid dehydrogenase. Disabling the metabolon contributes to BCAT2 deficiency-induced phenotypes, which can be reversed by BCAT1-mediated BCKA reamination. These findings establish a role for metabolon formation in BCAA metabolism in vivo and suggest a new strategy to modulate this pathway in diseases involving dysfunctional BCAA metabolism.
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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.