{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:16:11Z","timestamp":1792815371258,"version":"4.5.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000190","name":"University of Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1016\/j.jbc.2023.105375","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T02:39:02Z","timestamp":1697769542000},"page":"105375","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"title":["Loss of muscle PDH induces lactic acidosis and adaptive anaplerotic compensation via pyruvate-alanine cycling and glutaminolysis"],"prefix":"10.1016","volume":"299","author":[{"given":"Keshav","family":"Gopal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdualrahman Mohammed","family":"Abdualkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-2938","authenticated-orcid":false,"given":"Amanda A.","family":"Greenwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qutuba G.","family":"Karwi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq R.","family":"Altamimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Saed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Golam M.","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Darwesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3957-8988","authenticated-orcid":false,"given":"K. Lockhart","family":"Jamieson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryekjang","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Eaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Seubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Lopaschuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Ussher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Al Batran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2023.105375_bib1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.cmet.2017.04.015","article-title":"Metabolic flexibility in health and disease","volume":"25","author":"Goodpaster","year":"2017","journal-title":"Cell Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(63)91500-9","article-title":"The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus","volume":"1","author":"Randle","year":"1963","journal-title":"Lancet"},{"key":"10.1016\/j.jbc.2023.105375_bib3","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2337\/diabetes.49.5.677","article-title":"Fuel selection in human skeletal muscle in insulin resistance: a reexamination","volume":"49","author":"Kelley","year":"2000","journal-title":"Diabetes"},{"key":"10.1016\/j.jbc.2023.105375_bib4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1172\/JCI116603","article-title":"Interaction between glucose and free fatty acid metabolism in human skeletal muscle","volume":"92","author":"Kelley","year":"1993","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.jbc.2023.105375_bib5","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1172\/JCI117600","article-title":"Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus","volume":"94","author":"Kelley","year":"1994","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.jbc.2023.105375_bib6","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1172\/JCI114935","article-title":"Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus","volume":"86","author":"Kelley","year":"1990","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.jbc.2023.105375_bib7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmet.2007.10.013","article-title":"Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance","volume":"7","author":"Koves","year":"2008","journal-title":"Cell Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib8","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1006\/mgme.2001.3249","article-title":"Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development","volume":"74","author":"Johnson","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib9","doi-asserted-by":"crossref","first-page":"H946","DOI":"10.1152\/ajpheart.00363.2008","article-title":"Tissue-specific pyruvate dehydrogenase complex deficiency causes cardiac hypertrophy and sudden death of weaned male mice","volume":"295","author":"Sidhu","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.jbc.2023.105375_bib10","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nrc.2016.114","article-title":"From Krebs to clinic: glutamine metabolism to cancer therapy","volume":"16","author":"Altman","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.jbc.2023.105375_bib11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/S0753-3322(02)00285-8","article-title":"II. Glutamine and glutamate","volume":"56","author":"Tapiero","year":"2002","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jbc.2023.105375_bib12","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ccr.2012.09.021","article-title":"ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation","volume":"22","author":"Qing","year":"2012","journal-title":"Cancer Cell"},{"key":"10.1016\/j.jbc.2023.105375_bib13","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal muscle insulin resistance is the primary defect in type 2 diabetes","volume":"32 Suppl 2","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"10.1016\/j.jbc.2023.105375_bib14","doi-asserted-by":"crossref","first-page":"E1034","DOI":"10.1152\/ajpendo.00241.2018","article-title":"Defining the contribution of skeletal muscle pyruvate dehydrogenase \u03b11 to exercise performance and insulin action","volume":"315","author":"Svensson","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1126\/science.1218530","article-title":"Identification and functional expression of the mitochondrial pyruvate carrier","volume":"337","author":"Herzig","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.jbc.2023.105375_bib16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1126\/science.1218099","article-title":"A\u00a0mitochondrial pyruvate carrier required for pyruvate uptake in yeast, drosophila, and humans","volume":"337","author":"Bricker","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.jbc.2023.105375_bib17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev-nutr-120420-025558","article-title":"Ins and outs of the TCA cycle: the central role of anaplerosis","volume":"41","author":"Inigo","year":"2021","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.jbc.2023.105375_bib18","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cmet.2015.07.027","article-title":"Hepatic mitochondrial pyruvate carrier 1 is required for efficient regulation of gluconeogenesis and whole-body glucose homeostasis","volume":"22","author":"Gray","year":"2015","journal-title":"Cell Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib19","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cmet.2015.07.028","article-title":"Loss of mitochondrial pyruvate carrier 2 in the liver leads to defects in gluconeogenesis and compensation via pyruvate-alanine cycling","volume":"22","author":"McCommis","year":"2015","journal-title":"Cell Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib20","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1016\/j.celrep.2019.07.098","article-title":"Disrupting mitochondrial pyruvate uptake directs glutamine into the TCA cycle away from glutathione synthesis and impairs hepatocellular tumorigenesis","volume":"28","author":"Tompkins","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.jbc.2023.105375_bib21","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.45873","article-title":"Impaired skeletal muscle mitochondrial pyruvate uptake rewires glucose metabolism to drive whole-body leanness","volume":"8","author":"Sharma","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2023.105375_bib22","doi-asserted-by":"crossref","first-page":"E1151","DOI":"10.1152\/ajpendo.2001.281.6.E1151","article-title":"Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat\/low-carbohydrate diet","volume":"281","author":"Peters","year":"2001","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib23","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.2337\/diabetes.48.8.1593","article-title":"Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes","volume":"48","author":"Wu","year":"1999","journal-title":"Diabetes"},{"key":"10.1016\/j.jbc.2023.105375_bib24","doi-asserted-by":"crossref","first-page":"E46","DOI":"10.1152\/ajpendo.00536.2007","article-title":"Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice","volume":"295","author":"Jeoung","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev.bi.57.070188.001401","article-title":"Carnitine","volume":"57","author":"Bieber","year":"1988","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.jbc.2023.105375_bib26","doi-asserted-by":"crossref","first-page":"33899","DOI":"10.1074\/jbc.M402685200","article-title":"Redesign of carnitine acetyltransferase specificity by protein engineering","volume":"279","author":"Cordente","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2023.105375_bib27","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.cmet.2020.03.017","article-title":"Pimozide alleviates hyperglycemia in diet-induced obesity by inhibiting skeletal muscle ketone oxidation","volume":"31","author":"Al Batran","year":"2020","journal-title":"Cell Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1139\/cjpp-2017-0371","article-title":"Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development","volume":"96","author":"Aburasayn","year":"2018","journal-title":"Can J. Physiol. Pharmacol."},{"key":"10.1016\/j.jbc.2023.105375_bib29","doi-asserted-by":"crossref","first-page":"E425","DOI":"10.1152\/ajpendo.00206.2022","article-title":"Defective muscle ketone body oxidation disrupts BCAA catabolism by altering mitochondrial branched-chain aminotransferase","volume":"324","author":"Mechchate","year":"2023","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.molmet.2014.04.009","article-title":"Inactivation of the cardiomyocyte glucagon-like peptide-1 receptor (GLP-1R) unmasks cardiomyocyte-independent GLP-1R-mediated cardioprotection","volume":"3","author":"Ussher","year":"2014","journal-title":"Mol. Metab."},{"key":"10.1016\/j.jbc.2023.105375_bib31","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.jbc.2023.105375_bib32","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.2337\/db09-1293","article-title":"Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption","volume":"59","author":"Ussher","year":"2010","journal-title":"Diabetes"},{"key":"10.1016\/j.jbc.2023.105375_bib33","doi-asserted-by":"crossref","first-page":"418","DOI":"10.2337\/db16-0680","article-title":"Improved glucose homeostasis in obese mice treated with resveratrol is associated with alterations in the gut microbiome","volume":"66","author":"Sung","year":"2017","journal-title":"Diabetes"},{"key":"10.1016\/j.jbc.2023.105375_bib34","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aau8866","article-title":"Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity","volume":"11","author":"Saleme","year":"2019","journal-title":"Sci. Transl Med."},{"key":"10.1016\/j.jbc.2023.105375_bib35","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1042\/BCJ20170823","article-title":"Cytosolic carnitine acetyltransferase as a source of cytosolic acetyl-CoA: a possible mechanism for regulation of cardiac energy metabolism","volume":"475","author":"Altamimi","year":"2018","journal-title":"Biochem. J."},{"key":"10.1016\/j.jbc.2023.105375_bib36","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.yjmcc.2018.12.019","article-title":"Cardiac-specific deficiency of the mitochondrial calcium uniporter augments fatty acid oxidation and functional reserve","volume":"127","author":"Altamimi","year":"2019","journal-title":"J.\u00a0Mol. Cell. Cardiol."},{"key":"10.1016\/j.jbc.2023.105375_bib37","series-title":"Pseudomonas Methods and Protocols","first-page":"311","article-title":"Extraction and measurement of NAD (P)+ and NAD (P) H","author":"Kern","year":"2014"},{"key":"10.1016\/j.jbc.2023.105375_bib38","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.3390\/ijms20143502","article-title":"Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase ameliorates cardiac ischemia\/reperfusion injury by attenuating NLRP3 inflammasome activation","volume":"20","author":"Darwesh","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jbc.2023.105375_bib39","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nprot.2008.61","article-title":"Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells","volume":"3","author":"Kuznetsov","year":"2008","journal-title":"Nat. Protoc."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925823024031?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925823024031?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:44:34Z","timestamp":1762188274000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925823024031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":39,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["S0021925823024031"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2023.105375","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Loss of muscle PDH induces lactic acidosis and adaptive anaplerotic compensation via pyruvate-alanine cycling and glutaminolysis","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2023.105375","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"105375"}}