{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:38:48Z","timestamp":1792028328145,"version":"4.4.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2015,7,17]],"date-time":"2015-07-17T00:00:00Z","timestamp":1437091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Differ"],"published-print":{"date-parts":[[2016,2]]},"DOI":"10.1038\/cdd.2015.93","type":"journal-article","created":{"date-parts":[[2015,7,17]],"date-time":"2015-07-17T12:01:37Z","timestamp":1437134497000},"page":"270-278","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":441,"title":["Loss of cysteinyl-tRNA synthetase (CARS) induces the transsulfuration pathway and inhibits ferroptosis induced by cystine deprivation"],"prefix":"10.1038","volume":"23","author":[{"given":"M","family":"Hayano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W S","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C K","family":"Corn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N C","family":"Pagano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B R","family":"Stockwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,17]]},"reference":[{"key":"BFcdd201593_CR1","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nrn1100","volume":"4","author":"M Vila","year":"2003","unstructured":"Vila M, Przedborski S . Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 2003; 4: 365\u2013375.","journal-title":"Nat Rev Neurosci"},{"key":"BFcdd201593_CR2","doi-asserted-by":"publisher","first-page":"16836","DOI":"10.1073\/pnas.1415518111","volume":"111","author":"A Linkermann","year":"2014","unstructured":"Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C, De Zen F et al. Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci USA 2014; 111: 16836\u201316841.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcdd201593_CR3","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/ncb3064","volume":"16","author":"JP Friedmann Angeli","year":"2014","unstructured":"Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 2014; 16: 1180\u20131191.","journal-title":"Nat Cell Biol"},{"key":"BFcdd201593_CR4","doi-asserted-by":"publisher","first-page":"4551","DOI":"10.1021\/ja411006a","volume":"136","author":"R Skouta","year":"2014","unstructured":"Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc 2014; 136: 4551\u20134556.","journal-title":"J Am Chem Soc"},{"key":"BFcdd201593_CR5","doi-asserted-by":"crossref","first-page":"18480","DOI":"10.1016\/S0021-9258(18)51491-5","volume":"264","author":"S Bannai","year":"1989","unstructured":"Bannai S, Sato H, Ishii T, Sugita Y . Induction of cystine transport activity in human fibroblasts by oxygen. J Biol Chem 1989; 264: 18480\u201318484.","journal-title":"J Biol Chem"},{"key":"BFcdd201593_CR6","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","volume":"156","author":"WS Yang","year":"2014","unstructured":"Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 2014; 156: 317\u2013331.","journal-title":"Cell"},{"key":"BFcdd201593_CR7","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","volume":"15","author":"W Yang","year":"2008","unstructured":"Yang W, Stockwell B . Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol 2008; 15: 234\u2013245.","journal-title":"Chem Biol"},{"key":"BFcdd201593_CR8","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/S1535-6108(03)00050-3","volume":"3","author":"S Dolma","year":"2003","unstructured":"Dolma S, Lessnick S, Hahn W, Stockwell B . Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 2003; 3: 285\u2013296.","journal-title":"Cancer Cell"},{"key":"BFcdd201593_CR9","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nature05859","volume":"447","author":"N Yagoda","year":"2007","unstructured":"Yagoda N, von Rechenberg M, Zaganjor E, Bauer A, Yang W, Fridman D et al. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 2007; 447: 864\u2013868.","journal-title":"Nature"},{"key":"BFcdd201593_CR10","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1002\/ijc.28159","volume":"133","author":"C Louandre","year":"2013","unstructured":"Louandre C, Ezzoukhry Z, Godin C, Barbare J-C, Mazi\u00e8re J-C, Chauffert B et al. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int J Cancer 2013; 133: 1732\u20131742.","journal-title":"Int J Cancer"},{"key":"BFcdd201593_CR11","doi-asserted-by":"publisher","first-page":"e02523","DOI":"10.7554\/eLife.02523","volume":"3","author":"SJ Dixon","year":"2014","unstructured":"Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M et al. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife 2014; 3: e02523.","journal-title":"eLife"},{"key":"BFcdd201593_CR12","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"S Dixon","year":"2012","unstructured":"Dixon S, Lemberg K, Lamprecht M, Skouta R, Zaitsev E, Gleason C et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149: 1060\u20131072.","journal-title":"Cell"},{"key":"BFcdd201593_CR13","doi-asserted-by":"publisher","first-page":"R66","DOI":"10.1186\/gb-2006-7-7-r66","volume":"7","author":"M Boutros","year":"2006","unstructured":"Boutros M, Bras LP, Huber W . Analysis of cell-based RNAi screens. Genome Biol 2006; 7: R66.","journal-title":"Genome Biol"},{"key":"BFcdd201593_CR14","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/22780","volume":"400","author":"WC Hahn","year":"1999","unstructured":"Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA . Creation of human tumour cells with defined genetic elements. Nature 1999; 400: 464\u2013468.","journal-title":"Nature"},{"key":"BFcdd201593_CR15","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1002\/emmm.201100626","volume":"5","author":"P Yao","year":"2013","unstructured":"Yao P, Fox P . Aminoacyl-tRNA synthetases in medicine and disease. EMBO Mol Med 2013; 5: 332\u2013343.","journal-title":"EMBO Mol Med"},{"key":"BFcdd201593_CR16","doi-asserted-by":"publisher","first-page":"6124","DOI":"10.1021\/ja00799a053","volume":"95","author":"RH Abeles","year":"1973","unstructured":"Abeles RH, Walsh CT . Acetylenic enzyme inactivators. Inactivation of gamma-cystathionase, in vitro and in vivo, by propargylglycine. J Am Chem Soc 1973; 95: 6124\u20136125.","journal-title":"J Am Chem Soc"},{"key":"BFcdd201593_CR17","doi-asserted-by":"publisher","first-page":"7603","DOI":"10.1074\/jbc.M111.304576","volume":"287","author":"JG Dickhout","year":"2012","unstructured":"Dickhout JG, Carlisle RE, Jerome DE, Mohammed-Ali Z, Jiang H, Yang G et al. Integrated stress response modulates cellular redox state via induction of cystathionine gamma-lyase: cross-talk between integrated stress response and thiol metabolism. J Biol Chem 2012; 287: 7603\u20137614.","journal-title":"J Biol Chem"},{"key":"BFcdd201593_CR18","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nchembio.790","volume":"8","author":"TL Keller","year":"2012","unstructured":"Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J et al. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol 2012; 8: 311\u2013317.","journal-title":"Nat Chem Biol"},{"key":"BFcdd201593_CR19","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/nrm2956","volume":"11","author":"M Guo","year":"2010","unstructured":"Guo M, Yang XL, Schimmel P . New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev Mol Cell Biol 2010; 11: 668\u2013674.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcdd201593_CR20","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S0891-5849(97)00020-8","volume":"23","author":"CM Pereira","year":"1997","unstructured":"Pereira CM, Oliveira CR . Glutamate toxicity on a PC12 cell line involves glutathione (GSH) depletion and oxidative stress. Free Radic Biol Med 1997; 23: 637\u2013647.","journal-title":"Free Radic Biol Med"},{"key":"BFcdd201593_CR21","doi-asserted-by":"crossref","first-page":"12387","DOI":"10.1016\/S0021-9258(18)43284-X","volume":"256","author":"T Ishii","year":"1981","unstructured":"Ishii T, Bannai S, Sugita Y . Mechanism of growth stimulation of L1210 cells by 2-mercaptoethanol in vitro. Role of the mixed disulfide of 2-mercaptoethanol and cysteine. J Biol Chem 1981; 256: 12387\u201312392.","journal-title":"J Biol Chem"},{"key":"BFcdd201593_CR22","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00726-008-0199-2","volume":"37","author":"SS Palii","year":"2009","unstructured":"Palii SS, Kays CE, Deval C, Bruhat A, Fafournoux P, Kilberg MS . Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation. Amino Acids 2009; 37: 79\u201388.","journal-title":"Amino Acids"},{"key":"BFcdd201593_CR23","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1038\/ng.2732","volume":"45","author":"RP Mason","year":"2013","unstructured":"Mason RP, Casu M, Butler N, Breda C, Campesan S, Clapp J et al. Glutathione peroxidase activity is neuroprotective in models of Huntington's disease. Nat Genet 2013; 45: 1249\u20131254.","journal-title":"Nat Genet"},{"key":"BFcdd201593_CR24","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nature13136","volume":"509","author":"BD Paul","year":"2014","unstructured":"Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM et al. Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington's disease. Nature 2014; 509: 96\u2013100.","journal-title":"Nature"},{"key":"BFcdd201593_CR25","doi-asserted-by":"publisher","first-page":"4821","DOI":"10.1128\/AAC.49.12.4821-4833.2005","volume":"49","author":"JG Hurdle","year":"2005","unstructured":"Hurdle JG, O\u2019Neill AJ, Chopra I . Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents. Antimicrob Agents Chemother 2005; 49: 4821\u20134833.","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Cell Death &amp; Differentiation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/cdd201593.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cdd201593","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/cdd201593.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:09:52Z","timestamp":1684415392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cdd201593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,17]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["BFcdd201593"],"URL":"https:\/\/doi.org\/10.1038\/cdd.2015.93","relation":{},"ISSN":["1350-9047","1476-5403"],"issn-type":[{"value":"1350-9047","type":"print"},{"value":"1476-5403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,17]]},"assertion":[{"value":"6 January 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}