{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T22:33:21Z","timestamp":1778366001502,"version":"3.51.4"},"reference-count":31,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":902,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2,28]]},"abstract":"<jats:p>Mammalian cells adapt to different environmental conditions and alter cellular metabolic pathways to meet the energy demand for survival. Thus, the metabolic regulation of cells under special conditions, such as hypoxia, should be precisely regulated. During the metabolic regulation, mammalian target of rapamycin (mTOR) plays a vital role in the sensing of extracellular stimulations and regulating intracellular adaptations. Here, we report that mTOR complex 1 (mTORC1) signalling is a central regulator of lipid homoeostasis in lymphocytes. In hypoxia, mTORC1 activity is reduced and shifts lipid synthesis to lipid oxidation. Moreover, knockdown tuberous sclerosis complex 1 (TSC1) constitutively activates mTORC1 activity and impairs the hypoxia-induced metabolic shift. Therefore, TSC1 knockdown enhances hypoxia-induced cell death. Re-inactivation of mTORC1 activity via rapamycin may resist hypoxia-induced cell death in TSC1 knockdown lymphocytes. Our findings provide a deep insight into mTORC1 in the metabolic balance of lipid synthesis and oxidation, and imply that mTORC1 activity should be precisely regulated for the lipid homoeostasis in lymphocytes.<\/jats:p>","DOI":"10.1042\/bsr20160479","type":"journal-article","created":{"date-parts":[[2017,1,6]],"date-time":"2017-01-06T02:30:34Z","timestamp":1483669834000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["mTOR complex 1 signalling regulates the balance between lipid synthesis and oxidation in hypoxia lymphocytes"],"prefix":"10.1042","volume":"37","author":[{"given":"Geng","family":"Yin","sequence":"first","affiliation":[{"name":"Department of General Medicine, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-min","family":"Cen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi-bing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2017,2,3]]},"reference":[{"key":"2021111618410437100_B1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.tem.2009.03.003","article-title":"PXR and CAR in energy metabolism","volume":"20","author":"Wada","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"2021111618410437100_B2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13075-015-0542-4","article-title":"T-cell metabolism in autoimmune disease","volume":"17","author":"Yang","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"2021111618410437100_B3","doi-asserted-by":"crossref","first-page":"29655","DOI":"10.1074\/jbc.M212770200","article-title":"A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets.","volume":"278","author":"Arsham","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021111618410437100_B4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1189\/jlb.1212627","article-title":"Hypoxia: how does the monocyte-macrophage system respond to changes in oxygen availability?","volume":"95","author":"Strehl","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"2021111618410437100_B5","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1016\/S0021-9258(17)34720-8","article-title":"Control of fatty acid metabolism in ischemic and hypoxic hearts","volume":"253","author":"Whitmer","year":"1978","journal-title":"J. Biol. Chem."},{"key":"2021111618410437100_B6","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1038\/onc.2014.439","article-title":"SREBP maintains lipid biosynthesis and viability of cancer cells under lipid- and oxygen-deprived conditions and defines a gene signature associated with poor survival in glioblastoma multiforme","volume":"34","author":"Lewis","year":"2015","journal-title":"Oncogene"},{"key":"2021111618410437100_B7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/embor.2013.5","article-title":"The multifaceted role of mTORC1 in the control of lipid metabolism","volume":"14","author":"Ricoult","year":"2013","journal-title":"EMBO Rep."},{"key":"2021111618410437100_B8","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.ceb.2005.09.009","article-title":"Growing roles for the mTOR pathway","volume":"17","author":"Sarbassov","year":"2005","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021111618410437100_B9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","article-title":"Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase\/akt pathway","volume":"10","author":"Manning","year":"2002","journal-title":"Mol. Cell"},{"key":"2021111618410437100_B10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.molcel.2010.10.030","article-title":"mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1\u03b1","volume":"40","author":"Cam","year":"2010","journal-title":"Mol. Cell"},{"key":"2021111618410437100_B11","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":"Inoki","year":"2003","journal-title":"Cell"},{"key":"2021111618410437100_B12","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"2021111618410437100_B13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tem.2011.10.004","article-title":"SREBPs: metabolic integrators in physiology and metabolism","volume":"23","author":"Jeon","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"2021111618410437100_B14","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cmet.2008.07.007","article-title":"SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth","volume":"8","author":"Porstmann","year":"2008","journal-title":"Cell Metab."},{"key":"2021111618410437100_B15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cmet.2011.06.002","article-title":"Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways","volume":"14","author":"Yecies","year":"2011","journal-title":"Cell Metab."},{"key":"2021111618410437100_B16","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/j.metabol.2006.08.002","article-title":"Rapamycin-mediated inhibition of mammalian target of rapamycin in skeletal muscle cells reduces glucose utilization and increases fatty acid oxidation","volume":"55","author":"Sipula","year":"2006","journal-title":"Metabolism"},{"key":"2021111618410437100_B17","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/j.metabol.2007.06.016","article-title":"The mammalian target of rapamycin regulates lipid metabolism in primary cultures of rat hepatocytes","volume":"56","author":"Brown","year":"2007","journal-title":"Metabolism"},{"key":"2021111618410437100_B18","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1128\/MCB.00200-09","article-title":"Hypoxia-inducible factor 2 regulates hepatic lipid metabolism","volume":"29","author":"Rankin","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"2021111618410437100_B19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/cdd.2010.82","article-title":"The TSC1 and TSC2 tumor suppressors are required for proper ER stress response and protect cells from ER stress-induced apoptosis","volume":"18","author":"Kang","year":"2011","journal-title":"Cell Death Differ."},{"key":"2021111618410437100_B20","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1101\/gad.1256804","article-title":"Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1\/TSC2 tumor suppressor complex","volume":"18","author":"Brugarolas","year":"2004","journal-title":"Genes Dev."},{"key":"2021111618410437100_B21","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1126\/science.1228771","article-title":"Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis","volume":"339","author":"Robitaille","year":"2013","journal-title":"Science"},{"issue":"3","key":"2021111618410437100_B22","article-title":"Sterol regulatory element binding protein-dependent regulation of lipid synthesis supports cell survival and tumor growth","volume":"1","author":"Griffiths","year":"2013","journal-title":"Cancer Metab"},{"key":"2021111618410437100_B23","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.coi.2013.05.002","article-title":"mTOR and lymphocyte metabolism","volume":"25","author":"Zeng","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"2021111618410437100_B24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1152\/physiolgenomics.00293.2005","article-title":"Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1\u03b1","volume":"25","author":"Li","year":"2006","journal-title":"Physiol. Genomics"},{"key":"2021111618410437100_B25","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":"2012","journal-title":"Nature"},{"key":"2021111618410437100_B26","doi-asserted-by":"crossref","first-page":"ra17","DOI":"10.1126\/scisignal.2004785","article-title":"The adaptor protein p66Shc inhibits mTOR-dependent anabolic metabolism","volume":"7","author":"Soliman","year":"2014","journal-title":"Sci. Signal."},{"key":"2021111618410437100_B27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrm2672","article-title":"Molecular mechanisms of mTOR-mediated translational control","volume":"10","author":"Ma","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021111618410437100_B28","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrm4074","article-title":"Transcriptional regulation of hepatic lipogenesis","volume":"16","author":"Wang","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021111618410437100_B29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","article-title":"Activation of a metabolic gene regulatory network downstream of mTOR complex 1","volume":"39","author":"D\u00fcvel","year":"2010","journal-title":"Mol. Cell"},{"key":"2021111618410437100_B30","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nature14557","article-title":"The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1","volume":"524","author":"Han","year":"2015","journal-title":"Nature"},{"key":"2021111618410437100_B31","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrc704","article-title":"Hypoxia\u2013a key regulatory factor in tumour growth","volume":"2","author":"Harris","year":"2002","journal-title":"Nat. Rev. Cancer"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20160479\/428908\/bsr-2016-0479.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20160479\/428908\/bsr-2016-0479.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T19:09:26Z","timestamp":1637089766000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/37\/1\/BSR20160479\/56683\/mTOR-complex-1-signalling-regulates-the-balance"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,3]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,2,28]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20160479","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,3]]},"article-number":"BSR20160479"}}