{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:17:08Z","timestamp":1780510628831,"version":"3.54.1"},"reference-count":61,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":102,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA200653"],"award-info":[{"award-number":["R01CA200653"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","award":["P30CA013148"],"award-info":[{"award-number":["P30CA013148"]}],"id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008635","name":"University of Texas Health Science Center at San Antonio","doi-asserted-by":"publisher","award":["P30CA054174"],"award-info":[{"award-number":["P30CA054174"]}],"id":[{"id":"10.13039\/100008635","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM119557"],"award-info":[{"award-number":["R35GM119557"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>L-2-hydroxyglutarate (L-2HG) is an oncometabolite found elevated in renal tumors. However, this molecule might have physiological roles that extend beyond its association with cancer, as L-2HG levels are elevated in response to hypoxia and during Drosophila larval development. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH), and loss of L2HGDH leads to elevated L-2HG levels. Despite L2HGDH being highly expressed in the kidney, its role in renal metabolism has not been explored. Here, we report our findings utilizing a novel CRISPR\/Cas9 murine knockout model, with a specific focus on the role of L2HGDH in the kidney. Histologically, L2hgdh knockout kidneys have no demonstrable histologic abnormalities. However, GC-MS metabolomics demonstrates significantly reduced levels of the TCA cycle intermediate succinate in multiple tissues. Isotope labeling studies with [U-13C] glucose demonstrate that restoration of L2HGDH in renal cancer cells (which lowers L-2HG) leads to enhanced incorporation of label into TCA cycle intermediates. Subsequent biochemical studies demonstrate that L-2HG can inhibit the TCA cycle enzyme \u03b1-ketoglutarate dehydrogenase. Bioinformatic analysis of mRNA expression data from renal tumors demonstrates that L2HGDH is co-expressed with genes encoding TCA cycle enzymes as well as the gene encoding the transcription factor PGC-1\u03b1, which is known to regulate mitochondrial metabolism. Restoration of PGC-1\u03b1 in renal tumor cells results in increased L2HGDH expression with a concomitant reduction in L-2HG levels. Collectively, our analyses provide new insight into the physiological role of L2HGDH as well as mechanisms that promote L-2HG accumulation in disease states.<\/jats:p>","DOI":"10.1242\/dmm.045898","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T14:10:11Z","timestamp":1600092611000},"source":"Crossref","is-referenced-by-count":18,"title":["Teleological role of L-2-hydroxyglutarate dehydrogenase in the kidney"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-3416","authenticated-orcid":false,"given":"Garrett","family":"Brinkley","sequence":"first","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeyoung","family":"Nam","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhee","family":"Shim","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kirkman","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-9989","authenticated-orcid":false,"given":"Anirban","family":"Kundu","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Karki","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasaman","family":"Heidarian","sequence":"additional","affiliation":[{"name":"Indiana University, Bloomington, IN 47405, USA 2 Department of Biology ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-5683","authenticated-orcid":false,"given":"Jason M.","family":"Tennessen","sequence":"additional","affiliation":[{"name":"Indiana University, Bloomington, IN 47405, USA 2 Department of Biology ,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Duke University 3 Department of Pharmacology and Cancer Biology , , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7766-3502","authenticated-orcid":false,"given":"Jason W.","family":"Locasale","sequence":"additional","affiliation":[{"name":"Duke University 3 Department of Pharmacology and Cancer Biology , , Durham, NC 27710 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 4 Department of Pathology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Wei","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 4 Department of Pathology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gordetsky","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center 5 Departments of Pathology and Urology , , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-1206","authenticated-orcid":false,"given":"Teresa L.","family":"Johnson-Pais","sequence":"additional","affiliation":[{"name":"UT Health San Antonio 6 Department of Urology , , San Antonio, TX 78229 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Absher","sequence":"additional","affiliation":[{"name":"HudsonAlpha Institute for Biotechnology 7 , Huntsville, AL 35806 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-7902","authenticated-orcid":false,"given":"Dinesh","family":"Rakheja","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 8 Department of Pathology , , Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-3304","authenticated-orcid":false,"given":"Anil K.","family":"Challa","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 9 Department of Biology , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-6277","authenticated-orcid":false,"given":"Sunil","family":"Sudarshan","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Urology , , Birmingham, AL 35294 , USA"},{"name":"Birmingham VA Medical Center 10 , Birmingham, AL 35233 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"2024061302325326000_DMM045898C1","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1126\/science.287.5454.848","article-title":"Mutations in Sdhd, a mitochondrial complex II gene, in hereditary paraganglioma","volume":"287","author":"Baysal","year":"2000","journal-title":"Science"},{"key":"2024061302325326000_DMM045898C2","doi-asserted-by":"publisher","first-page":"6888","DOI":"10.1158\/0008-5472.CAN-11-1011","article-title":"PGC1alpha promotes tumor growth by inducing gene expression programs supporting lipogenesis","volume":"71","author":"Bhalla","year":"2011","journal-title":"Cancer Res."},{"key":"2024061302325326000_DMM045898C3","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1038\/s41467-017-02181-0","article-title":"Genomic regression analysis of coordinated expression","volume":"8","author":"Cai","year":"2017","journal-title":"Nat. Commun."},{"key":"2024061302325326000_DMM045898C4","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1152\/japplphysiol.01231.2007","article-title":"Muscle-specific expression of PPAR\u03b3 coactivator-1\u03b1 improves exercise performance and increases peak oxygen uptake","volume":"104","author":"Calvo","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"2024061302325326000_DMM045898C5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nature12222","article-title":"Comprehensive molecular characterization of clear cell renal cell carcinoma","volume":"499","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nature"},{"key":"2024061302325326000_DMM045898C6","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"2024061302325326000_DMM045898C101","doi-asserted-by":"publisher","first-page":"e0155812","DOI":"10.1371\/journal.pone.0155812","article-title":"Novel hypomorphic alleles of the mouse tyrosinase gene induced by CRISPR-Cas9 nucleases cause non-albino pigmentation phenotypes","volume":"11","author":"Challa","year":"2016","journal-title":"PLoS One"},{"key":"2024061302325326000_DMM045898C102","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1038\/nprot.2011.375","article-title":"Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry","volume":"6","author":"Chan","year":"2011","journal-title":"Nat. Protoc."},{"key":"2024061302325326000_DMM045898C7","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2024061302325326000_DMM045898C8","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.cmet.2018.07.020","article-title":"Isotope tracing of human clear cell renal cell carcinomas demonstrates suppressed glucose oxidation in vivo","volume":"28","author":"Courtney","year":"2018","journal-title":"Cell Metab."},{"key":"2024061302325326000_DMM045898C9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/BF02312543","article-title":"L-2-Hydroxyglutaric aciduria: an inborn error of metabolism","volume":"3","author":"Duran","year":"1980","journal-title":"J. Inherit. Metab. Dis."},{"key":"2024061302325326000_DMM045898C10","doi-asserted-by":"publisher","first-page":"pl1","DOI":"10.1126\/scisignal.6273er1","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"2024061302325326000_DMM045898C103","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1203\/00006450-199309000-00007","article-title":"Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias","volume":"34","author":"Gibson","year":"1993","journal-title":"Pediatr. Res."},{"key":"2024061302325326000_DMM045898C11","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1056\/NEJMc0910063","article-title":"Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms","volume":"362","author":"Green","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2024061302325326000_DMM045898C12","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1055\/s-2008-1081217","article-title":"L-2-hydroxyglutaric aciduria and brain tumors in children with mutations in the L2HGDH gene: neuroimaging findings","volume":"39","author":"Haliloglu","year":"2008","journal-title":"Neuropediatrics"},{"key":"2024061302325326000_DMM045898C13","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nbt.2501","article-title":"Efficient genome editing in zebrafish using a CRISPR-Cas system","volume":"31","author":"Hwang","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2024061302325326000_DMM045898C14","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/nchembio.2307","article-title":"L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH","volume":"13","author":"Intlekofer","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"2024061302325326000_DMM045898C15","doi-asserted-by":"publisher","first-page":"13904","DOI":"10.1073\/pnas.1308335110","article-title":"Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system","volume":"110","author":"Jao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061302325326000_DMM045898C16","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","article-title":"Toward understanding the origin and evolution of cellular organisms","volume":"28","author":"Kanehisa","year":"2019","journal-title":"Protein Sci."},{"key":"2024061302325326000_DMM045898C17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2024061302325326000_DMM045898C18","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gky962","article-title":"New approach for understanding genome variations in KEGG","volume":"47","author":"Kanehisa","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2024061302325326000_DMM045898C19","doi-asserted-by":"publisher","first-page":"10436","DOI":"10.1073\/pnas.1601650113","article-title":"Oncometabolite d-2-hydroxyglutarate impairs \u03b1-ketoglutarate dehydrogenase and contractile function in rodent heart","volume":"113","author":"Karlstaedt","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061302325326000_DMM045898C20","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cmet.2006.02.002","article-title":"HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia","volume":"3","author":"Kim","year":"2006","journal-title":"Cell Metab."},{"key":"2024061302325326000_DMM045898C21","doi-asserted-by":"publisher","first-page":"C1074","DOI":"10.1152\/ajpcell.00391.2004","article-title":"Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism","volume":"288","author":"Koves","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2024061302325326000_DMM045898C22","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s10545-012-9462-5","article-title":"Progress in understanding 2-hydroxyglutaric acidurias","volume":"35","author":"Kranendijk","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"2024061302325326000_DMM045898C23","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2024061302325326000_DMM045898C24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.celrep.2015.06.006","article-title":"Suppression of PGC-1\u03b1 is critical for reprogramming oxidative metabolism in renal cell carcinoma","volume":"12","author":"Lagory","year":"2015","journal-title":"Cell Rep"},{"key":"2024061302325326000_DMM045898C25","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1073\/pnas.1614102114","article-title":"Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061302325326000_DMM045898C26","doi-asserted-by":"publisher","first-page":"dmm035337","DOI":"10.1242\/dmm.035337","article-title":"A Drosophila model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation","volume":"11","author":"Li","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"2024061302325326000_DMM045898C100","doi-asserted-by":"publisher","first-page":"e57847","DOI":"10.3791\/57847","article-title":"Preparation of Drosophila larval samples for gas chromatography-mass spectrometry (GC-MS)-based metabolomics","author":"Li","year":"2018","journal-title":"J. Vis. Exp."},{"key":"2024061302325326000_DMM045898C27","doi-asserted-by":"publisher","first-page":"W199","DOI":"10.1093\/nar\/gkz401","article-title":"WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2024061302325326000_DMM045898C28","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1074\/mcp.M114.044859","article-title":"High-resolution metabolomics with acyl-CoA profiling reveals widespread remodeling in response to diet","volume":"14","author":"Liu","year":"2015","journal-title":"Mol. Cell. Proteomics"},{"key":"2024061302325326000_DMM045898C29","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1021\/ac403845u","article-title":"Development and quantitative evaluation of a high-resolution metabolomics technology","volume":"86","author":"Liu","year":"2014","journal-title":"Anal. Chem."},{"key":"2024061302325326000_DMM045898C30","doi-asserted-by":"publisher","first-page":"e00492-16","DOI":"10.1128\/MCB.00492-16","article-title":"L2hgdh Deficiency Accumulates l-2-Hydroxyglutarate with Progressive Leukoencephalopathy and Neurodegeneration","volume":"37","author":"Ma","year":"2017","journal-title":"Mol. Cell. Biol."},{"key":"2024061302325326000_DMM045898C31","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1056\/NEJMoa0903840","article-title":"Recurring mutations found by sequencing an acute myeloid leukemia genome","volume":"361","author":"Mardis","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"2024061302325326000_DMM045898C32","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cell.2018.08.038","article-title":"Transaminase inhibition by 2-hydroxyglutarate impairs glutamate biosynthesis and redox homeostasis in glioma","volume":"175","author":"McBrayer","year":"2018","journal-title":"Cell"},{"key":"2024061302325326000_DMM045898C33","doi-asserted-by":"publisher","first-page":"20188","DOI":"10.1074\/jbc.M116.738799","article-title":"Acidic pH is a metabolic switch for 2-hydroxyglutarate generation and signaling","volume":"291","author":"Nadtochiy","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2024061302325326000_DMM045898C34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.matbio.2020.01.001","article-title":"PGC1\u03b1 suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression","volume":"89","author":"Nam","year":"2020","journal-title":"Matrix Biol."},{"key":"2024061302325326000_DMM045898C35","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/81551","article-title":"Mutations in SDHC cause autosomal dominant paraganglioma, type 3","volume":"26","author":"Niemann","year":"2000","journal-title":"Nat. Genet."},{"key":"2024061302325326000_DMM045898C36","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.cmet.2015.06.021","article-title":"Hypoxia-mediated increases in L-2-hydroxyglutarate coordinate the metabolic response to reductive stress","volume":"22","author":"Oldham","year":"2015","journal-title":"Cell Metab."},{"key":"2024061302325326000_DMM045898C37","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.cmet.2006.01.012","article-title":"HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption","volume":"3","author":"Papandreou","year":"2006","journal-title":"Cell Metab."},{"key":"2024061302325326000_DMM045898C38","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1126\/science.1164382","article-title":"An integrated genomic analysis of human glioblastoma multiforme","volume":"321","author":"Parsons","year":"2008","journal-title":"Science"},{"key":"2024061302325326000_DMM045898C104","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jchromb.2008.04.033","article-title":"Gas chromatography\/mass spectrometry in metabolic profiling of biological fluids","volume":"871","author":"Pasikanti","year":"2008","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"2024061302325326000_DMM045898C39","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s13277-010-0125-6","article-title":"Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate","volume":"32","author":"Rakheja","year":"2011","journal-title":"Tumour Biol."},{"key":"2024061302325326000_DMM045898C40","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s10545-007-0487-0","article-title":"L-2-hydroxyglutaric aciduria, a defect of metabolite repair","volume":"30","author":"Rzem","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"2024061302325326000_DMM045898C41","doi-asserted-by":"publisher","first-page":"e0119540","DOI":"10.1371\/journal.pone.0119540","article-title":"A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair","volume":"10","author":"Rzem","year":"2015","journal-title":"PLoS ONE"},{"key":"2024061302325326000_DMM045898C42","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1093\/jxb\/err371","article-title":"Frontiers in metabolic reconstruction and modeling of plant genomes","volume":"63","author":"Seaver","year":"2012","journal-title":"J. Exp. Bot."},{"key":"2024061302325326000_DMM045898C43","doi-asserted-by":"publisher","first-page":"6433","DOI":"10.1158\/1078-0432.CCR-18-1727","article-title":"Biochemical and epigenetic insights into L-2-hydroxyglutarate, a potential therapeutic target in renal cancer","volume":"24","author":"Shelar","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"2024061302325326000_DMM045898C44","doi-asserted-by":"publisher","first-page":"483","DOI":"10.18632\/oncoscience.165","article-title":"Another small molecule in the oncometabolite mix: L-2-Hydroxyglutarate in kidney cancer","volume":"2","author":"Shim","year":"2015","journal-title":"Oncoscience"},{"key":"2024061302325326000_DMM045898C45","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1158\/2159-8290.CD-13-0696","article-title":"L-2-Hydroxyglutarate: an epigenetic modifier and putative oncometabolite in renal cancer","volume":"4","author":"Shim","year":"2014","journal-title":"Cancer Discov"},{"key":"2024061302325326000_DMM045898C46","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cell.2017.11.031","article-title":"R-2HG exhibits anti-tumor activity by targeting FTO\/m6A\/MYC\/CEBPA signaling","volume":"172","author":"Su","year":"2018","journal-title":"Cell"},{"key":"2024061302325326000_DMM045898C47","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1021\/acschembio.6b00290","article-title":"Lactate dehydrogenase C produces S-2-hydroxyglutarate in mouse testis","volume":"11","author":"Teng","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"2024061302325326000_DMM045898C48","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/ng849","article-title":"Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer","volume":"30","author":"Tomlinson","year":"2002","journal-title":"Nat. Genet."},{"key":"2024061302325326000_DMM045898C49","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1002\/1531-8249(199901)45:1&lt;111::AID-ART17&gt;3.0.CO;2-N","article-title":"D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity?","volume":"45","author":"van der Knaap","year":"1999","journal-title":"Ann. Neurol."},{"key":"2024061302325326000_DMM045898C50","doi-asserted-by":"publisher","first-page":"W77","DOI":"10.1093\/nar\/gkt439","article-title":"WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013","volume":"41","author":"Wang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2024061302325326000_DMM045898C51","doi-asserted-by":"publisher","first-page":"W130","DOI":"10.1093\/nar\/gkx356","article-title":"WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit","volume":"45","author":"Wang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2024061302325326000_DMM045898C52","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.gde.2019.04.001","article-title":"Engineering CRISPR mouse models of cancer","volume":"54","author":"Weber","year":"2019","journal-title":"Curr. Opin. Genet. Dev."},{"key":"2024061302325326000_DMM045898C53","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.semnephrol.2019.12.002","article-title":"Reprogramming of metabolism in kidney cancer","volume":"40","author":"Wettersten","year":"2020","journal-title":"Semin. Nephrol."},{"key":"2024061302325326000_DMM045898C54","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ccr.2010.12.014","article-title":"Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of \u03b1-ketoglutarate-dependent dioxygenases","volume":"19","author":"Xu","year":"2011","journal-title":"Cancer Cell"},{"key":"2024061302325326000_DMM045898C55","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 and IDH2 mutations in gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"2024061302325326000_DMM045898C56","doi-asserted-by":"publisher","first-page":"W741","DOI":"10.1093\/nar\/gki475","article-title":"WebGestalt: an integrated system for exploring gene sets in various biological contexts","volume":"33","author":"Zhang","year":"2005","journal-title":"Nucleic Acids Res."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.045898","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.045898\/3484337\/dmm045898.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.045898\/2066025\/dmm_045898v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.045898\/3484337\/dmm045898.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:33:12Z","timestamp":1718245992000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/13\/11\/dmm045898\/225776\/Teleological-role-of-L-2-hydroxyglutarate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,1]]},"references-count":61,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.045898","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2020,11,1]]},"article-number":"dmm045898"}}