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DOI | 10.1126/science.aan6298 |
Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes | |
Abu-Remaileh, Monther1,2,3,4,5; Wyant, Gregory A.1,2,3,4,5; Kim, Choah1,2,3,4,5; Laqtom, Nouf N.1,2,3,4,5; Abbasi, Maria1,2,3,4,5; Chan, Sze Ham1,2; Freinkman, Elizaveta1,2,6; Sabatini, David M.1,2,3,4,5 | |
2017-11-10 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6364页码:807-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, many lysosomal amino acids are in rapid exchange with those in the cytosol. Loss of lysosomal acidification through inhibition of the vacuolar H+ -adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most metabolites but had no effect on those of the majority of essential amino acids. Instead, nutrient starvation regulates the lysosomal concentrations of these amino acids, an effect we traced to regulation of the mechanistic target of rapamycin (mTOR) pathway. Inhibition of mTOR strongly reduced the lysosomal efflux of most essential amino acids, converting the lysosome into a cellular depot for them. These results reveal the dynamic nature of lysosomal metabolites and that V-ATPase-and mTOR-dependent mechanisms exist for controlling lysosomal amino acid efflux. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000414847100049 |
WOS关键词 | UBIQUITIN PROTEASOME SYSTEM ; ANTITUMOR-ACTIVITY ; RAG GTPASES ; AUTOPHAGY ; COMPLEX ; PROTEIN ; SUFFICIENCY ; INHIBITORS ; MEMBRANE ; NUTRIENT |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197291 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA; 2.MIT, Dept Biol, 9 Cambridge Ctr, Cambridge, MA 02142 USA; 3.MIT, Dept Biol, Howard Hughes Med Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA; 4.Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA; 5.Broad Inst Harvard & Massachusetts Inst Technol, 7 Cambridge Ctr, Cambridge, MA 02142 USA; 6.Metabolon Inc, Res Triangle Pk, NC 27709 USA |
推荐引用方式 GB/T 7714 | Abu-Remaileh, Monther,Wyant, Gregory A.,Kim, Choah,et al. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes[J]. SCIENCE,2017,358(6364):807-+. |
APA | Abu-Remaileh, Monther.,Wyant, Gregory A..,Kim, Choah.,Laqtom, Nouf N..,Abbasi, Maria.,...&Sabatini, David M..(2017).Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes.SCIENCE,358(6364),807-+. |
MLA | Abu-Remaileh, Monther,et al."Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes".SCIENCE 358.6364(2017):807-+. |
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