{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:15:05Z","timestamp":1792271705608,"version":"4.4.0"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6582","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2022,2,18]]},"abstract":"<jats:p>\n            Adaptation to nutrient scarcity involves an orchestrated response of metabolic and signaling pathways to maintain homeostasis. We find that in the fat body of fasting\n            <jats:italic>Drosophila<\/jats:italic>\n            , lysosomal export of cystine coordinates remobilization of internal nutrient stores with reactivation of the growth regulator target of rapamycin complex 1 (TORC1). Mechanistically, cystine was reduced to cysteine and metabolized to acetyl-coenzyme A (acetyl-CoA) by promoting CoA metabolism. In turn, acetyl-CoA retained carbons from alternative amino acids in the form of tricarboxylic acid cycle intermediates and restricted the availability of building blocks required for growth. This process limited TORC1 reactivation to maintain autophagy and allowed animals to cope with starvation periods. We propose that cysteine metabolism mediates a communication between lysosomes and mitochondria, highlighting how changes in diet divert the fate of an amino acid into a growth suppressive program.\n          <\/jats:p>","DOI":"10.1126\/science.abc4203","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T18:57:32Z","timestamp":1645124252000},"source":"Crossref","is-referenced-by-count":78,"title":["Lysosomal cystine mobilization shapes the response of TORC1 and tissue growth to fasting"],"prefix":"10.1126","volume":"375","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-7694","authenticated-orcid":true,"given":"Patrick","family":"Jouandin","sequence":"first","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3702-7528","authenticated-orcid":true,"given":"Zvonimir","family":"Marelja","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IHU Imagine \u2013 Institut des maladies g\u00e9n\u00e9tiques, Laboratory of Epithelial Biology and Disease, 75015 Paris, France."},{"name":"Institute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Hsin","family":"Shih","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9852-8329","authenticated-orcid":true,"given":"Andrey A.","family":"Parkhitko","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Dambowsky","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IHU Imagine \u2013 Institut des maladies g\u00e9n\u00e9tiques, Laboratory of Epithelial Biology and Disease, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7450-2589","authenticated-orcid":true,"given":"John M.","family":"Asara","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02175, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-839X","authenticated-orcid":true,"given":"Ivan","family":"Nemazanyy","sequence":"additional","affiliation":[{"name":"Platform for Metabolic Analyses, Structure F\u00e9d\u00e9rative de Recherche Necker, INSERM US24\/CNRS UMS 3633, Paris 75015, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1122-9017","authenticated-orcid":true,"given":"Christian C.","family":"Dibble","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA."},{"name":"Department of Pathology, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3959-6350","authenticated-orcid":true,"given":"Matias","family":"Simons","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM, IHU Imagine \u2013 Institut des maladies g\u00e9n\u00e9tiques, Laboratory of Epithelial Biology and Disease, 75015 Paris, France."},{"name":"Institute of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-472X","authenticated-orcid":true,"given":"Norbert","family":"Perrimon","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.03.014"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.07.027"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.07.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.07.009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.21228"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00369-y"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar2663"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09076"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00713-X"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.08.002"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006036"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.63"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506736200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014090937"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02536-7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0498-319"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1102008108"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13034"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.6.1682S"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)81430-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2280545"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2680077"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.062"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.64.1.227"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144504"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0125-0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614102114"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.03.013"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.029"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.042"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.048"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.043"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200217666151210124713"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.208"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161226225"},{"key":"e_1_3_3_37_2","first-page":"1097","article-title":"N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis","volume":"29","author":"Pache de Faria Guimaraes L.","year":"2014","unstructured":"L. Pache de Faria Guimaraes, A. C. Seguro, M. H. Shimizu, L. A. Lopes Neri, N. M. Sumita, A. C. de Bragan\u00e7a, R. Aparecido Volpini, T. R. Cunha Sanches, F. A. Macaferri da Fonseca, C. A. Moreira Filho, M. H. Vaisbich, N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis. Pediatr. Nephrol. 29, 1097\u20131102 (2014). 24326786","journal-title":"Pediatr. Nephrol."},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101561"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002392"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.03.016"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.03.017"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.088757"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067308"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2731"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-006-9018-4"},{"key":"e_1_3_3_46_2","doi-asserted-by":"crossref","unstructured":"G. M. Mackay L. Zheng N. J. F. van den Broek E. Gottlieb \u201cAnalysis of cell metabolism using LC-MS and isotope tracers \u201d in Metabolic Analysis Using Stable Isotopes C. M. Metallo Ed. (Academic 2015) Methods in Enzymology series vol. 561 pp. 171\u2013196.","DOI":"10.1016\/bs.mie.2015.05.016"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.03.015"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.2.331"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051411"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02797462"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.03.013"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.abc4203","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T22:30:26Z","timestamp":1705357826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.abc4203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":50,"journal-issue":{"issue":"6582","published-print":{"date-parts":[[2022,2,18]]}},"alternative-id":["10.1126\/science.abc4203"],"URL":"https:\/\/doi.org\/10.1126\/science.abc4203","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"article-number":"eabc4203"}}