Insights into the Metabolic Regulation by GATOR1 in Response to Amino Acid Signaling

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dc.contributor.advisorLiu, Yien
dc.contributor.committeeMemberTu, Benjaminen
dc.contributor.committeeMemberPhillips, Margaret A.en
dc.contributor.committeeMemberGoodman, Joel M.en
dc.creatorChen, Junen
dc.creator.orcid0000-0002-5814-1653
dc.date.accessioned2019-09-03T19:57:28Z
dc.date.available2019-09-03T19:57:28Z
dc.date.created2017-08
dc.date.issued2017-07-27
dc.date.submittedAugust 2017
dc.date.updated2019-09-03T19:57:28Z
dc.description.abstractThe GATOR1/SEACIT complex consisting of Iml1-Npr2-Npr3 inhibits Target of Rapamycin Complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, yeast mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite hallmarks of increased TORC1 signaling. Such mutants perceive they are amino acid-replete and thus repress metabolic activities that are important for achieving this state. I find that npr2∆ mutants have defective mitochondrial TCA cycle activity and retrograde response. Supplementation of glutamine, and especially aspartate, which are nitrogen-containing forms of TCA cycle intermediates, rescue growth of npr2∆ mutants. These amino acids are then consumed in biosynthetic pathways that require nitrogen to support proliferative metabolism. Our findings reveal that negative regulators of TORC1 such as GATOR1/SEACIT regulate the cataplerotic synthesis of these amino acids from the TCA cycle in tune with the amino acid and nitrogen status of cells.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1117308710
dc.identifier.urihttps://hdl.handle.net/2152.5/7202
dc.language.isoenen
dc.subjectCitric Acid Cycleen
dc.subjectMitochondriaen
dc.subjectMultiprotein Complexesen
dc.subjectSaccharomyces cerevisiaeen
dc.subjectSaccharomyces cerevisiae Proteinsen
dc.titleInsights into the Metabolic Regulation by GATOR1 in Response to Amino Acid Signalingen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineIntegrative Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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