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dc.contributor.authorChan, Sze Ham
dc.contributor.authorFreinkman, Elizaveta
dc.contributor.authorAbu-Remaileh, Monther
dc.contributor.authorWyant, Gregory Andrew
dc.contributor.authorKim, Choah
dc.contributor.authorLaqtom, Nouf N
dc.contributor.authorAbbasi, Maria
dc.contributor.authorSabatini, David
dc.date.accessioned2019-01-08T16:18:33Z
dc.date.available2019-01-08T16:18:33Z
dc.date.issued2017-11
dc.date.submitted2017-05
dc.identifier.issn0036-8075
dc.identifier.issn1095-9203
dc.identifier.urihttp://hdl.handle.net/1721.1/119871
dc.description.abstractThe 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.en_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1126/SCIENCE.AAN6298en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleLysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomesen_US
dc.typeArticleen_US
dc.identifier.citationAbu-Remaileh, Monther et al. “Lysosomal Metabolomics Reveals V-ATPase- and mTOR-Dependent Regulation of Amino Acid Efflux from Lysosomes.” Science 358, 6364 (October 2017): 807–813 © 2017 American Association for the Advancement of Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorAbu-Remaileh, Monther
dc.contributor.mitauthorWyant, Gregory Andrew
dc.contributor.mitauthorKim, Choah
dc.contributor.mitauthorLaqtom, Nouf N
dc.contributor.mitauthorAbbasi, Maria
dc.contributor.mitauthorSabatini, David
dc.relation.journalScienceen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-12-19T15:31:26Z
dspace.orderedauthorsAbu-Remaileh, Monther; Wyant, Gregory A.; Kim, Choah; Laqtom, Nouf N.; Abbasi, Maria; Chan, Sze Ham; Freinkman, Elizaveta; Sabatini, David M.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-4642-3706
dc.identifier.orcidhttps://orcid.org/0000-0002-1446-7256
mit.licenseOPEN_ACCESS_POLICYen_US


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