{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T08:37:01Z","timestamp":1770280621154,"version":"3.49.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA297993"],"award-info":[{"award-number":["R01CA297993"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA197398"],"award-info":[{"award-number":["R01CA197398"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA270588"],"award-info":[{"award-number":["R21CA270588"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA252430"],"award-info":[{"award-number":["R21CA252430"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA263133"],"award-info":[{"award-number":["R21CA263133"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Autophagy is a highly conserved, intracellular recycling process by which cytoplasmic contents are degraded in the lysosome. This process occurs at a low level constitutively; however, it is induced robustly in response to stressors, in particular, starvation of critical nutrients such as amino acids and glucose. That said, the relative contribution of these inputs is ambiguous, and many starvation medias are poorly defined or devoid of multiple nutrients. Here, we set out to create a quantitative dataset of autophagy across multiple stages in single, living cells, measured under normal growth conditions and during nutrient starvation of amino acids or glucose. We found that autophagy is induced by starvation of amino acids, but not glucose, in U2OS cells, and that MTORC1-mediated ULK1 regulation and autophagy are tightly linked to amino acid levels. While autophagy is engaged immediately during amino acid starvation, a heightened response occurs during a period marked by transcriptional upregulation of autophagy genes during sustained starvation. Finally, we demonstrated that cells immediately return to their initial, low-autophagy state when nutrients are restored, highlighting the dynamic relationship between autophagy and environmental conditions.<\/jats:p>","DOI":"10.1371\/journal.pone.0340957","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:21:47Z","timestamp":1770229307000},"page":"e0340957","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative and temporal analysis of autophagy: Differential Response to amino acid and glucose starvation"],"prefix":"10.1371","volume":"21","author":[{"given":"Katie R.","family":"Martin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie L.","family":"Celano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica D.","family":"Guillaume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan D.","family":"Sheldon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell G.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-5679","authenticated-orcid":true,"given":"Jeffrey P.","family":"MacKeigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"issue":"13","key":"pone.0340957.ref001","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1101\/gad.219642.113","article-title":"Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis","volume":"27","author":"JY Guo","year":"2013","journal-title":"Genes Dev"},{"issue":"15","key":"pone.0340957.ref002","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1101\/gad.283416.116","article-title":"Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells","volume":"30","author":"JY Guo","year":"2016","journal-title":"Genes Dev"},{"issue":"8","key":"pone.0340957.ref003","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1158\/2159-8290.CD-14-0363","article-title":"Autophagy is required for glucose homeostasis and lung tumor maintenance","volume":"4","author":"G Karsli-Uzunbas","year":"2014","journal-title":"Cancer Discov"},{"key":"pone.0340957.ref004","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1038\/ncomms4056","article-title":"A dual role for autophagy in a murine model of lung cancer","volume":"5","author":"S Rao","year":"2014","journal-title":"Nat Commun"},{"issue":"11","key":"pone.0340957.ref005","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1158\/2159-8290.CD-13-0397","article-title":"Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors","volume":"3","author":"AM Strohecker","year":"2013","journal-title":"Cancer Discov"},{"issue":"2","key":"pone.0340957.ref006","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2019.03.037","article-title":"Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunity","volume":"27","author":"L DeVorkin","year":"2019","journal-title":"Cell Rep"},{"issue":"7637","key":"pone.0340957.ref007","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature20815","article-title":"Microenvironmental autophagy promotes tumour growth","volume":"541","author":"NS Katheder","year":"2017","journal-title":"Nature"},{"issue":"7806","key":"pone.0340957.ref008","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41586-020-2229-5","article-title":"Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I","volume":"581","author":"K Yamamoto","year":"2020","journal-title":"Nature"},{"issue":"3","key":"pone.0340957.ref009","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1158\/2159-8290.CD-17-0952","article-title":"Autophagy Sustains Pancreatic Cancer Growth through Both Cell-Autonomous and Nonautonomous Mechanisms","volume":"8","author":"A Yang","year":"2018","journal-title":"Cancer Discov"},{"issue":"18","key":"pone.0340957.ref010","doi-asserted-by":"crossref","first-page":"12297","DOI":"10.1074\/jbc.M900573200","article-title":"ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy","volume":"284","author":"IG Ganley","year":"2009","journal-title":"J Biol Chem"},{"issue":"7","key":"pone.0340957.ref011","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1091\/mbc.e08-12-1248","article-title":"Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy","volume":"20","author":"N Hosokawa","year":"2009","journal-title":"Mol Biol Cell"},{"issue":"7","key":"pone.0340957.ref012","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1091\/mbc.e08-12-1249","article-title":"ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery","volume":"20","author":"CH Jung","year":"2009","journal-title":"Mol Biol Cell"},{"issue":"4","key":"pone.0340957.ref013","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1083\/jcb.200803137","article-title":"Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum","volume":"182","author":"EL Axe","year":"2008","journal-title":"J Cell Biol"},{"issue":"4","key":"pone.0340957.ref014","doi-asserted-by":"crossref","first-page":"506","DOI":"10.4161\/auto.6.4.11863","article-title":"Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation","volume":"6","author":"HEJ Polson","year":"2010","journal-title":"Autophagy"},{"issue":"18","key":"pone.0340957.ref015","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1016\/j.febslet.2007.06.040","article-title":"Human WIPI-1 puncta-formation: a novel assay to assess mammalian autophagy","volume":"581","author":"T Proikas-Cezanne","year":"2007","journal-title":"FEBS Lett"},{"issue":"1","key":"pone.0340957.ref016","doi-asserted-by":"crossref","first-page":"6750","DOI":"10.1038\/s41467-021-26999-x","article-title":"The autophagy protein ATG9A enables lipid mobilization from lipid droplets","volume":"12","author":"E Mailler","year":"2021","journal-title":"Nat Commun"},{"issue":"10","key":"pone.0340957.ref017","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1091\/mbc.e11-09-0746","article-title":"Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy","volume":"23","author":"A Orsi","year":"2012","journal-title":"Mol Biol Cell"},{"issue":"22","key":"pone.0340957.ref018","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2022.10.017","article-title":"ATG9A and ATG2A form a heteromeric complex essential for autophagosome formation","volume":"82","author":"AR van Vliet","year":"2022","journal-title":"Mol Cell"},{"issue":"7","key":"pone.0340957.ref019","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.febslet.2010.01.020","article-title":"New insights into the function of Atg9","volume":"584","author":"JL Webber","year":"2010","journal-title":"FEBS Lett"},{"key":"pone.0340957.ref020","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.1242\/jcs.03172","article-title":"Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes","volume":"119","author":"ARJ Young","year":"2006","journal-title":"J Cell Sci"},{"issue":"6700","key":"pone.0340957.ref021","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/26506","article-title":"A protein conjugation system essential for autophagy","volume":"395","author":"N Mizushima","year":"1998","journal-title":"Nature"},{"issue":"6811","key":"pone.0340957.ref022","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/35044114","article-title":"A ubiquitin-like system mediates protein lipidation","volume":"408","author":"Y Ichimura","year":"2000","journal-title":"Nature"},{"issue":"21","key":"pone.0340957.ref023","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing","volume":"19","author":"Y Kabeya","year":"2000","journal-title":"EMBO J"},{"issue":"5","key":"pone.0340957.ref024","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1091\/mbc.e07-12-1257","article-title":"The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy","volume":"19","author":"N Fujita","year":"2008","journal-title":"Mol Biol Cell"},{"issue":"7","key":"pone.0340957.ref025","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1091\/mbc.e08-12-1250","article-title":"An Atg1\/Atg13 complex with multiple roles in TOR-mediated autophagy regulation","volume":"20","author":"Y-Y Chang","year":"2009","journal-title":"Mol Biol Cell"},{"key":"pone.0340957.ref026","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev-pharmtox-010611-134537","article-title":"AMPK and mTOR in cellular energy homeostasis and drug targets","volume":"52","author":"K Inoki","year":"2012","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"2","key":"pone.0340957.ref027","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"DM Gwinn","year":"2008","journal-title":"Mol Cell"},{"issue":"5","key":"pone.0340957.ref028","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","article-title":"TSC2 mediates cellular energy response to control cell growth and survival","volume":"115","author":"K Inoki","year":"2003","journal-title":"Cell"},{"issue":"6016","key":"pone.0340957.ref029","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1126\/science.1196371","article-title":"Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy","volume":"331","author":"DF Egan","year":"2011","journal-title":"Science"},{"issue":"2","key":"pone.0340957.ref030","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"J Kim","year":"2011","journal-title":"Nat Cell Biol"},{"issue":"13","key":"pone.0340957.ref031","doi-asserted-by":"crossref","DOI":"10.1016\/j.devcel.2021.05.010","article-title":"Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner","volume":"56","author":"C Karabiyik","year":"2021","journal-title":"Dev Cell"},{"issue":"27","key":"pone.0340957.ref032","doi-asserted-by":"crossref","first-page":"11121","DOI":"10.1073\/pnas.1107969108","article-title":"Ammonia-induced autophagy is independent of ULK1\/ULK2 kinases","volume":"108","author":"H Cheong","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"pone.0340957.ref033","doi-asserted-by":"crossref","first-page":"16736","DOI":"10.1074\/jbc.M113.525782","article-title":"Glucose starvation inhibits autophagy via vacuolar hydrolysis and induces plasma membrane internalization by down-regulating recycling","volume":"289","author":"MJ Lang","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0340957.ref034","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1038\/s41467-023-38401-z","article-title":"Redefining the role of AMPK in autophagy and the energy stress response","volume":"14","author":"J-M Park","year":"2023","journal-title":"Nat Commun"},{"issue":"42","key":"pone.0340957.ref035","doi-asserted-by":"crossref","first-page":"30387","DOI":"10.1074\/jbc.M113.490581","article-title":"Glucose-starved cells do not engage in prosurvival autophagy","volume":"288","author":"S Ram\u00edrez-Peinado","year":"2013","journal-title":"J Biol Chem"},{"issue":"9","key":"pone.0340957.ref036","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1080\/15548627.2024.2355074","article-title":"Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation","volume":"20","author":"D Kazyken","year":"2024","journal-title":"Autophagy"},{"issue":"5","key":"pone.0340957.ref037","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.01058.2024","article-title":"Multifaceted role of AMPK in autophagy: more than a simple trigger?","volume":"329","author":"M Mandic","year":"2025","journal-title":"Am J Physiol Cell Physiol"},{"issue":"10","key":"pone.0340957.ref038","doi-asserted-by":"crossref","DOI":"10.1128\/MCB.00023-18","article-title":"AMPK Inhibits ULK1-Dependent Autophagosome Formation and Lysosomal Acidification via Distinct Mechanisms","volume":"38","author":"C Nwadike","year":"2018","journal-title":"Molecular and Cellular Biology"},{"issue":"8","key":"pone.0340957.ref039","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202309145","article-title":"AMPK regulates phagophore-to-autophagosome maturation","volume":"223","author":"C Barnaba","year":"2024","journal-title":"J Cell Biol"},{"issue":"3","key":"pone.0340957.ref040","article-title":"Contrasting views on the role of AMPK in autophagy","volume":"46","author":"D-H Kim","year":"2024","journal-title":"Bioessays"},{"issue":"1","key":"pone.0340957.ref041","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1","volume":"17","author":"DJ Klionsky","year":"2021","journal-title":"Autophagy"},{"issue":"17","key":"pone.0340957.ref042","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1093\/emboj\/19.17.4577","article-title":"Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells","volume":"19","author":"DJ Gillooly","year":"2000","journal-title":"EMBO J"},{"issue":"1","key":"pone.0340957.ref043","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1038\/s41467-020-16886-2","article-title":"Leucine regulates autophagy via acetylation of the mTORC1 component raptor","volume":"11","author":"SM Son","year":"2020","journal-title":"Nat Commun"},{"issue":"11","key":"pone.0340957.ref044","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/s41419-021-04121-9","article-title":"A gene toolbox for monitoring autophagy transcription","volume":"12","author":"M Bordi","year":"2021","journal-title":"Cell Death Dis"},{"issue":"6","key":"pone.0340957.ref045","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1038\/s41418-023-01162-9","article-title":"Transcriptional regulation of autophagy and its implications in human disease","volume":"30","author":"Y Lei","year":"2023","journal-title":"Cell Death Differ"},{"issue":"3","key":"pone.0340957.ref046","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1097-2765(03)00105-9","article-title":"An integrated stress response regulates amino acid metabolism and resistance to oxidative stress","volume":"11","author":"HP Harding","year":"2003","journal-title":"Mol Cell"},{"key":"pone.0340957.ref047","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainres.2008.10.050","article-title":"Identification of new Nerve Growth Factor-responsive immediate-early genes","volume":"1249","author":"TF Dijkmans","year":"2009","journal-title":"Brain Res"},{"issue":"3","key":"pone.0340957.ref048","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physiolgenomics.00217.2009","article-title":"Expression profiling after activation of amino acid deprivation response in HepG2 human hepatoma cells","volume":"41","author":"J Shan","year":"2010","journal-title":"Physiol Genomics"},{"key":"pone.0340957.ref049","unstructured":"Human Autophagy Database (HADb). http:\/\/autophagy.lu\/index.html 2023. 2023 November 30."},{"issue":"11","key":"pone.0340957.ref050","doi-asserted-by":"crossref","DOI":"10.1002\/jcp.31366","article-title":"No energy, no autophagy-Mechanisms and therapeutic implications of autophagic response energy requirements","volume":"239","author":"M Mandic","year":"2024","journal-title":"J Cell Physiol"},{"issue":"4","key":"pone.0340957.ref051","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00280-010-1391-0","article-title":"2-Deoxy-D-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion","volume":"67","author":"H Xi","year":"2011","journal-title":"Cancer Chemother Pharmacol"},{"issue":"11","key":"pone.0340957.ref052","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.tcb.2019.08.009","article-title":"The Rise of Physiologic Media","volume":"29","author":"JR Cantor","year":"2019","journal-title":"Trends Cell Biol"},{"issue":"2","key":"pone.0340957.ref053","article-title":"An mTORC1-to-CDK1 Switch Maintains Autophagy Suppression during Mitosis","volume":"77","author":"RI Odle","year":"2020","journal-title":"Mol Cell"},{"issue":"9","key":"pone.0340957.ref054","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/j.1582-4934.2011.01339.x","article-title":"Freeze-fracture replica immunolabelling reveals human WIPI-1 and WIPI-2 as membrane proteins of autophagosomes","volume":"15","author":"T Proikas-Cezanne","year":"2011","journal-title":"J Cell Mol Med"},{"issue":"5","key":"pone.0340957.ref055","doi-asserted-by":"crossref","first-page":"452","DOI":"10.4161\/auto.4451","article-title":"Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3","volume":"3","author":"S Kimura","year":"2007","journal-title":"Autophagy"},{"issue":"6","key":"pone.0340957.ref056","doi-asserted-by":"crossref","first-page":"764","DOI":"10.4161\/auto.6.6.12709","article-title":"Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins","volume":"6","author":"E Itakura","year":"2010","journal-title":"Autophagy"},{"issue":"3","key":"pone.0340957.ref057","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1083\/jcb.200712064","article-title":"FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells","volume":"181","author":"T Hara","year":"2008","journal-title":"J Cell Biol"},{"key":"pone.0340957.ref058","doi-asserted-by":"crossref","first-page":"15637","DOI":"10.1038\/ncomms15637","article-title":"WIPI3 and WIPI4 \u03b2-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy","volume":"8","author":"D Bakula","year":"2017","journal-title":"Nat Commun"},{"key":"pone.0340957.ref059","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1242\/jcs.080341","article-title":"Identification of PTPsigma as an autophagic phosphatase","volume":"124","author":"KR Martin","year":"2011","journal-title":"J Cell Sci"},{"issue":"1","key":"pone.0340957.ref060","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4161\/auto.22532","article-title":"Computational model for autophagic vesicle dynamics in single cells","volume":"9","author":"KR Martin","year":"2013","journal-title":"Autophagy"},{"issue":"9","key":"pone.0340957.ref061","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.cmet.2022.07.012","article-title":"Carbon source availability drives nutrient utilization in CD8(+) T cells","volume":"34","author":"I Kaymak","year":"2022","journal-title":"Cell Metab"},{"issue":"5","key":"pone.0340957.ref062","article-title":"Metabolic Profiling Using Stable Isotope Tracing Reveals Distinct Patterns of Glucose Utilization by Physiologically Activated CD8+ T Cells","volume":"51","author":"EH Ma","year":"2019","journal-title":"Immunity"},{"issue":"1","key":"pone.0340957.ref063","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1080\/15476286.2023.2204586","article-title":"Prior metabolite extraction fully preserves RNAseq quality and enables integrative multi-\u2019omics analysis of the liver metabolic response to viral infection","volume":"20","author":"ZB Madaj","year":"2023","journal-title":"RNA Biol"},{"issue":"3","key":"pone.0340957.ref064","doi-asserted-by":"crossref","DOI":"10.1242\/bio.059647","article-title":"New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape","volume":"12","author":"CR Schultz","year":"2023","journal-title":"Biol Open"},{"issue":"1","key":"pone.0340957.ref065","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Y Zhou","year":"2019","journal-title":"Nat Commun"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0340957","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:21:59Z","timestamp":1770229319000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0340957"}},"subtitle":[],"editor":[{"given":"Mohamed","family":"Abdelkarim","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":65,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0340957","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]}}}