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dc.contributor.authorFreinkman, Elizaveta
dc.contributor.authorBirsoy, Kıvanç
dc.contributor.authorChen, Walter W.
dc.contributor.authorWang, Tim
dc.contributor.authorSabatini, David
dc.date.accessioned2018-07-05T13:50:12Z
dc.date.available2018-07-05T13:50:12Z
dc.date.issued2016-08
dc.date.submitted2016-06
dc.identifier.issn0092-8674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/116785
dc.description.abstractMitochondria house metabolic pathways that impact most aspects of cellular physiology. While metabolite profiling by mass spectrometry is widely applied at the whole-cell level, it is not routinely possible to measure the concentrations of small molecules in mammalian organelles. We describe a method for the rapid and specific isolation of mitochondria and use it in tandem with a database of predicted mitochondrial metabolites (“MITObolome”) to measure the matrix concentrations of more than 100 metabolites across various states of respiratory chain (RC) function. Disruption of the RC reveals extensive compartmentalization of mitochondrial metabolism and signatures unique to the inhibition of each RC complex. Pyruvate enables the proliferation of RC-deficient cells but has surprisingly limited effects on matrix contents. Interestingly, despite failing to restore matrix NADH/NAD balance, pyruvate does increase aspartate, likely through the exchange of matrix glutamate for cytosolic aspartate. We demonstrate the value of mitochondrial metabolite profiling and describe a strategy applicable to other organelles.en_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/J.CELL.2016.07.040en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleAbsolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolismen_US
dc.typeArticleen_US
dc.identifier.citationChen, Walter W. et al. “Absolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolism.” Cell 166, 5 (August 2016): 1324–1337 © 2016 Elsevier Incen_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & 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.mitauthorChen, Walter W.
dc.contributor.mitauthorWang, Tim
dc.contributor.mitauthorSabatini, David
dc.relation.journalCellen_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.updated2018-07-03T18:30:52Z
dspace.orderedauthorsChen, Walter W.; Freinkman, Elizaveta; Wang, Tim; Birsoy, Kıvanç; Sabatini, David M.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7043-5013
dc.identifier.orcidhttps://orcid.org/0000-0002-4227-5163
dc.identifier.orcidhttps://orcid.org/0000-0002-1446-7256
mit.licensePUBLISHER_CCen_US


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