{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:11:13Z","timestamp":1788988273806,"version":"build-2803163510"},"reference-count":32,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82325038"],"award-info":[{"award-number":["82325038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82530094"],"award-info":[{"award-number":["82530094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303227"],"award-info":[{"award-number":["82303227"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Innovation"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.xinn.2026.101365","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:09:05Z","timestamp":1775030945000},"page":"101365","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells"],"prefix":"10.1016","volume":"7","author":[{"given":"Xuexue","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengjiao","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewei","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxin","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-0846","authenticated-orcid":false,"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xinn.2026.101365_bib1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tcb.2025.07.005","article-title":"NADH reductive stress drives metabolic reprogramming","volume":"36","author":"Yang","year":"2026","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.xinn.2026.101365_bib2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1126\/science.aad4017","article-title":"Complementation of mitochondrial electron transport chain by manipulation of the NAD+\/NADH ratio","volume":"352","author":"Titov","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.xinn.2026.101365_bib3","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20191226","article-title":"Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth","volume":"217","author":"Liu","year":"2020","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.xinn.2026.101365_bib4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/ars.2007.1672","article-title":"NAD+\/NADH and NADP+\/NADPH in cellular functions and cell death: regulation and biological consequences","volume":"10","author":"Ying","year":"2008","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.xinn.2026.101365_bib5","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1042\/BJ20061638","article-title":"The power to reduce: pyridine nucleotides--small molecules with a multitude of functions","volume":"402","author":"Pollak","year":"2007","journal-title":"Biochem. J."},{"key":"10.1016\/j.xinn.2026.101365_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"10.1016\/j.xinn.2026.101365_bib7","doi-asserted-by":"crossref","first-page":"7508","DOI":"10.1074\/jbc.TM117.000258","article-title":"Spatiotemporal compartmentalization of hepatic NADH and NADPH metabolism","volume":"293","author":"Goodman","year":"2018","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.xinn.2026.101365_bib8","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic glycolysis: meeting the metabolic requirements of cell proliferation","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"10.1016\/j.xinn.2026.101365_bib9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41556-024-01549-x","article-title":"AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress","volume":"27","author":"Zhai","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.xinn.2026.101365_bib10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nature10642","article-title":"Reductive carboxylation supports growth in tumour cells with defective mitochondria","volume":"481","author":"Mullen","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.xinn.2026.101365_bib11","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10602","article-title":"Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia","volume":"481","author":"Metallo","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.xinn.2026.101365_bib12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41467-018-08033-9","article-title":"Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia","volume":"10","author":"Wang","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.xinn.2026.101365_bib13","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/nrc.2016.85","article-title":"Altered metabolite levels in cancer: implications for tumour biology and cancer therapy","volume":"16","author":"Sullivan","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.xinn.2026.101365_bib14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-020-2337-2","article-title":"Hepatic NADH reductive stress underlies common variation in metabolic traits","volume":"583","author":"Goodman","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.xinn.2026.101365_bib15","doi-asserted-by":"crossref","first-page":"7031","DOI":"10.1038\/s41467-022-34850-0","article-title":"Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress","volume":"13","author":"Yang","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.xinn.2026.101365_bib16","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.cmet.2023.11.010","article-title":"ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits","volume":"36","author":"Singh","year":"2024","journal-title":"Cell Metab."},{"key":"10.1016\/j.xinn.2026.101365_bib17","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.cmet.2021.06.013","article-title":"Glycerol-3-phosphate biosynthesis regenerates cytosolic NAD(+) to alleviate mitochondrial disease","volume":"33","author":"Liu","year":"2021","journal-title":"Cell Metab."},{"key":"10.1016\/j.xinn.2026.101365_bib18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature17399","article-title":"Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1","volume":"532","author":"Chouchani","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.xinn.2026.101365_bib19","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1089\/ars.2021.0111","article-title":"Mitochondrial NAD(P)(+) Transhydrogenase: From Molecular Features to Physiology and Disease","volume":"36","author":"Francisco","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.xinn.2026.101365_bib20","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s42255-019-0043-x","article-title":"NADPH production by the oxidative pentose-phosphate pathway supports folate metabolism","volume":"1","author":"Chen","year":"2019","journal-title":"Nat. Metab."},{"key":"10.1016\/j.xinn.2026.101365_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102587","article-title":"Glucose-6-phosphate dehydrogenase exerts antistress effects independently of its enzymatic activity","volume":"298","author":"Jin","year":"2022","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.xinn.2026.101365_bib22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41392-020-00399-x","article-title":"Glucose-6-phosphate dehydrogenase neutralizes stresses by supporting reductive glutamine metabolism and AMPK activation","volume":"6","author":"Zhong","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.xinn.2026.101365_bib23","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.cell.2015.07.017","article-title":"Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells","volume":"162","author":"Sullivan","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.xinn.2026.101365_bib24","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/nchembio.2454","article-title":"A genetically encoded tool for manipulation of NADP(+)\/NADPH in living cells","volume":"13","author":"Cracan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.xinn.2026.101365_bib25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cmet.2015.04.009","article-title":"SoNar, a Highly Responsive NAD+\/NADH Sensor, Allows High-Throughput Metabolic Screening of Anti-tumor Agents","volume":"21","author":"Zhao","year":"2015","journal-title":"Cell Metab."},{"key":"10.1016\/j.xinn.2026.101365_bib26","doi-asserted-by":"crossref","DOI":"10.1002\/advs.201903483","article-title":"Targeting Pyruvate Carboxylase by a Small Molecule Suppresses Breast Cancer Progression","volume":"7","author":"Lin","year":"2020","journal-title":"Adv. Sci."},{"key":"10.1016\/j.xinn.2026.101365_bib27","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1016\/j.molcel.2021.08.028","article-title":"A hydride transfer complex reprograms NAD metabolism and bypasses senescence","volume":"81","author":"Igelmann","year":"2021","journal-title":"Mol. Cell"},{"key":"10.1016\/j.xinn.2026.101365_bib28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cmet.2011.09.004","article-title":"Genetically encoded fluorescent sensors for intracellular NADH detection","volume":"14","author":"Zhao","year":"2011","journal-title":"Cell Metab."},{"key":"10.1016\/j.xinn.2026.101365_bib29","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI72873","article-title":"Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation","volume":"125","author":"Sellers","year":"2015","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.xinn.2026.101365_bib30","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","article-title":"Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer","volume":"13","author":"Gross","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.xinn.2026.101365_bib31","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.molcel.2020.12.012","article-title":"Increased demand for NAD(+) relative to ATP drives aerobic glycolysis","volume":"81","author":"Luengo","year":"2021","journal-title":"Mol. Cell"},{"key":"10.1016\/j.xinn.2026.101365_bib32","doi-asserted-by":"crossref","first-page":"8682","DOI":"10.1038\/s41467-024-52968-1","article-title":"Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition","volume":"15","author":"Del Prado","year":"2024","journal-title":"Nat. Commun."}],"container-title":["The Innovation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666675826001128?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666675826001128?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:52:29Z","timestamp":1788987149000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666675826001128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["S2666675826001128"],"URL":"https:\/\/doi.org\/10.1016\/j.xinn.2026.101365","relation":{},"ISSN":["2666-6758"],"issn-type":[{"value":"2666-6758","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells","name":"articletitle","label":"Article Title"},{"value":"The Innovation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xinn.2026.101365","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc. on behalf of Youth Innovation Co., Ltd.","name":"copyright","label":"Copyright"}],"article-number":"101365"}}