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dc.contributor.authorKe, Hangjun
dc.contributor.authorLewis, Ian A.
dc.contributor.authorMorrisey, Joanne M.
dc.contributor.authorMcLean, Kyle J.
dc.contributor.authorPainter, Heather J.
dc.contributor.authorMather, Michael W.
dc.contributor.authorJacobs-Lorena, Marcelo
dc.contributor.authorVaidya, Akhil B.
dc.contributor.authorMaddur Ganesan, Suresh
dc.contributor.authorLlinas, Manuel
dc.date.accessioned2016-03-14T23:29:34Z
dc.date.available2016-03-14T23:29:34Z
dc.date.issued2015-04
dc.date.submitted2015-02
dc.identifier.issn22111247
dc.identifier.urihttp://hdl.handle.net/1721.1/101701
dc.description.abstractNew antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO) lines that delete six of the eight mitochondrial tricarboxylic acid (TCA) cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate-dehydrogenase-deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of [superscript 13]C-isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development.en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.celrep.2015.03.011en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleGenetic Investigation of Tricarboxylic Acid Metabolism during the Plasmodium falciparum Life Cycleen_US
dc.typeArticleen_US
dc.identifier.citationKe, Hangjun, Ian A. Lewis, Joanne M. Morrisey, Kyle J. McLean, Suresh M. Ganesan, Heather J. Painter, Michael W. Mather, Marcelo Jacobs-Lorena, Manuel Llinas, and Akhil B. Vaidya. “Genetic Investigation of Tricarboxylic Acid Metabolism During the Plasmodium Falciparum Life Cycle.” Cell Reports 11, no. 1 (April 2015): 164–174.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.contributor.mitauthorMaddur Ganesan, Sureshen_US
dc.relation.journalCell Reportsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsKe, Hangjun; Lewis, Ian A.; Morrisey, Joanne M.; McLean, Kyle J.; Ganesan, Suresh M.; Painter, Heather J.; Mather, Michael W.; Jacobs-Lorena, Marcelo; Llinas, Manuel; Vaidya, Akhil B.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7779-2216
mit.licensePUBLISHER_CCen_US


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