Show simple item record

dc.contributor.authorFendt, Sarah-Maria
dc.contributor.authorBell, Eric L.
dc.contributor.authorMayers, Jared R.
dc.contributor.authorVokes, Natalie I.
dc.contributor.authorStephanopoulos, Gregory
dc.contributor.authorKeibler, Mark Andrew
dc.contributor.authorWasylenko, Thomas Michael
dc.contributor.authorGuarente, Leonard Pershing
dc.contributor.authorVander Heiden, Matthew G.
dc.contributor.authorOlenchock, Benjamin
dc.date.accessioned2014-11-07T19:00:02Z
dc.date.available2014-11-07T19:00:02Z
dc.date.issued2013-07
dc.date.submitted2012-12
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1721.1/91505
dc.description.abstractReductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ketoglutarate/citrate ratio is changed due to an altered acetyl-CoA to citrate conversion, and demonstrate that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio. Thus, targeting reductive glutamine conversion for a therapeutic benefit might require distinct modulations of metabolite concentrations rather than targeting the upstream signalling, which only indirectly affects the process.en_US
dc.description.sponsorshipGerman Science Foundation (Grant FE1185)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship F32 CA132358)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)en_US
dc.description.sponsorshipDamon Runyon Cancer Research Foundationen_US
dc.description.sponsorshipBurroughs Wellcome Funden_US
dc.description.sponsorshipSmith Family Foundationen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant 1R01CA160458-01A1)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/ncomms3236en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleReductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cellsen_US
dc.typeArticleen_US
dc.identifier.citationFendt, Sarah-Maria, Eric L. Bell, Mark A. Keibler, Benjamin A. Olenchock, Jared R. Mayers, Thomas M. Wasylenko, Natalie I. Vokes, Leonard Guarente, Matthew G. Vander Heiden, and Gregory Stephanopoulos. “Reductive Glutamine Metabolism Is a Function of the α-Ketoglutarate to Citrate Ratio in Cells.” Nature Communications 4 (July 31, 2013).en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.mitauthorFendt, Sarah-Mariaen_US
dc.contributor.mitauthorKeibler, Mark Andrewen_US
dc.contributor.mitauthorWasylenko, Thomas Michaelen_US
dc.contributor.mitauthorStephanopoulos, Gregoryen_US
dc.contributor.mitauthorBell, Eric L.en_US
dc.contributor.mitauthorMayers, Jared R.en_US
dc.contributor.mitauthorGuarente, Leonard Pershingen_US
dc.contributor.mitauthorVander Heiden, Matthew G.en_US
dc.contributor.mitauthorOlenchock, Benjaminen_US
dc.contributor.mitauthorVokes, Natalie I.en_US
dc.relation.journalNature Communicationsen_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
dspace.orderedauthorsFendt, Sarah-Maria; Bell, Eric L.; Keibler, Mark A.; Olenchock, Benjamin A.; Mayers, Jared R.; Wasylenko, Thomas M.; Vokes, Natalie I.; Guarente, Leonard; Heiden, Matthew G. Vander; Stephanopoulos, Gregoryen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-8956-5117
dc.identifier.orcidhttps://orcid.org/0000-0002-8607-1787
dc.identifier.orcidhttps://orcid.org/0000-0002-6702-4192
dc.identifier.orcidhttps://orcid.org/0000-0002-5410-6543
dc.identifier.orcidhttps://orcid.org/0000-0003-4064-2510
dc.identifier.orcidhttps://orcid.org/0000-0001-6909-4568
mit.licensePUBLISHER_POLICYen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record