{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Patrick M"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","U.S. Department of Defense","NCI NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health","Cancer Prevention and Research Institute of Texas"],"pagination":["1775-1791"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11977170"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["4(12)"],"pubmed_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 "],"journal":["Nature metabolism"],"pubmed_title":["Metabolon formation regulates branched-chain amino acid oxidation and homeostasis."],"pmcid":["PMC11977170"],"funding_grant_id":["R35CA22044901","RP220375","R01 CA259581","R01CA230631","R01DK111430","R01 CA230631","RP180778","R01CA259581","RP180504","R21 AI158240","RP220337","RP190417","R01 DK111430","R21AI158240","PR191670"],"pubmed_authors":["Zhang G","Wynn RM","Cao H","DeBerardinis RJ","Chen M","Kaphle P","Patrick M","Gu Z","Cai F","Ni M","Xu J","Vu H","Zhang Y","Chuang DT","Gao X"],"additional_accession":[]},"is_claimable":false,"name":"Metabolon formation regulates branched-chain amino acid oxidation and homeostasis.","description":"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 ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-07-07T03:10:02.776Z","creation":"2025-07-07T03:10:02.776Z"},"accession":"S-EPMC11977170","cross_references":{"pubmed":["36443523"],"doi":["10.1038/s42255-022-00689-4"]}}