2025
1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion
RUZ-MALDONADO I, CARDONE R, MERRINS M, KIBBEY R. 1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion. Diabetes 2025, 74 DOI: 10.2337/db25-1824-p.Peer-Reviewed Original ResearchPyruvate kinaseATP/ADP ratioMitochondrial OXPHOSHuman isletsBeta-cellsIntact miceOxygen consumption rateKATP channel closureInsulin secretionMitochondrial membrane potentialPlasma membrane depolarizationDose-dependent mannerIntramitochondrial ADPADP availabilityHyperpolarized mitochondriaInitial insulin secretionKATP channelsMitochondrial hyperpolarizationOXPHOS inhibitionINS-1Pyruvate metabolismETC complexesMembrane depolarizationATP synthesisOXPHOS
2022
Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS
Shi X, Reinstadler B, Shah H, To TL, Byrne K, Summer L, Calvo SE, Goldberger O, Doench JG, Mootha VK, Shen H. Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. Nature Communications 2022, 13: 2483. PMID: 35513392, PMCID: PMC9072411, DOI: 10.1038/s41467-022-30126-9.Peer-Reviewed Original ResearchConceptsDe novo purine biosynthesisMitochondrial iron uptakeStructure-guided mutagenesisNovo purine biosynthesisMetabolic stateMitochondrial glutathione transportGlutathione importGenetic interactionsGenetic perturbationsDifferent metabolic environmentsFitness defectsLack of substrateGene interactionsMitochondrial OXPHOSMitochondrial membranePurine biosynthesisCarrier familyTransport assaysKO cellsIron uptakeGlutathione transportTransport activityIron homeostasisGlutathione homeostasisGenes
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