2025
Pantothenate kinase is an effective target for antifungal therapy
Regan J, DeJarnette C, Reitler P, Gihaz S, Srivastava A, Ge W, Tucker K, Peters T, Meibohm B, Ben Mamoun C, Fortwendel J, Hevener K, Palmer G. Pantothenate kinase is an effective target for antifungal therapy. Cell Chemical Biology 2025, 32: 710-721.e6. PMID: 40378822, DOI: 10.1016/j.chembiol.2025.04.007.Peer-Reviewed Original ResearchConceptsPantothenate kinasePathogenic yeast Candida albicansDisseminated C. albicans infectionYeast Candida albicansIn vivo antifungal efficacyChemical-genetic approachBroad-spectrum antifungalAntifungal therapeuticsCoA productionCandida albicansMammalian hostsAntifungal therapyCoenzyme ASmall molecule inhibitorsAntifungal efficacyPanKEssential cofactorChemical probesMolecule inhibitorsKinaseLiving organismsPantothenateMouse modelEffective targetVirulence
2022
Redesigning therapies for pantothenate kinase–associated neurodegeneration
Munshi MI, Yao SJ, Mamoun C. Redesigning therapies for pantothenate kinase–associated neurodegeneration. Journal Of Biological Chemistry 2022, 298: 101577. PMID: 35041826, PMCID: PMC8861153, DOI: 10.1016/j.jbc.2022.101577.Peer-Reviewed Original ResearchConceptsPantothenate kinase-associated neurodegenerationCellular metabolic processesMore common diseasesMetabolic processesPhysiological importancePANK2 genePantothenate kinaseCoenzyme ACoenzyme A.Rare genetic disorderCommon neurodegenerative diseaseNeurodegenerative diseasesGenetic disordersNeurodegenerationNew avenuesBiosynthesisKinaseGenesNew lightFuture investigationsCofactorMutationsCommon diseaseEnzymeAlzheimer's disease
2020
Cysteine depletion induces pancreatic tumor ferroptosis in mice
Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, Decker AR, Sastra SA, Palermo CF, Andrade LR, Sajjakulnukit P, Zhang L, Tolstyka ZP, Hirschhorn T, Lamb C, Liu T, Gu W, Seeley ES, Stone E, Georgiou G, Manor U, Iuga A, Wahl GM, Stockwell BR, Lyssiotis CA, Olive KP. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science 2020, 368: 85-89. PMID: 32241947, PMCID: PMC7681911, DOI: 10.1126/science.aaw9872.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesLipid reactive oxygen speciesPancreatic ductal adenocarcinomaLipid ROS productionAmino acid cysteineCell deathPDAC growthCysteine depletionCoenzyme APDAC cellsTumor ferroptosisROS productionFerroptosisCysteineOxygen speciesCatastrophic accumulationTranslatable meansCancer mortalityDuctal adenocarcinomaLeading causeSystem xTumor typesSubunitsSpeciesDeletion
2019
Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses
Langston PK, Nambu A, Jung J, Shibata M, Aksoylar HI, Lei J, Xu P, Doan MT, Jiang H, MacArthur MR, Gao X, Kong Y, Chouchani ET, Locasale JW, Snyder NW, Horng T. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nature Immunology 2019, 20: 1186-1195. PMID: 31384058, PMCID: PMC6707851, DOI: 10.1038/s41590-019-0453-7.Peer-Reviewed Original ResearchConceptsAcetyl coenzyme AGlycerol phosphate shuttleInduction of genesCoenzyme APhosphate shuttleAcetylation of histonesHistone acetylationInflammatory responseMitochondrial glycerolGPD2Inflammatory mediatorsMicrobial infectionsMicrobial stimulationGenesHost defenseGlucose oxidationAcetylationOxidative metabolismBacterial lipopolysaccharideSustained inflammationMacrophage activationHistonesDetrimental effectsMacrophagesAcute exposure
2017
The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation
Chiu JE, Thekkiniath J, Choi JY, Perrin BA, Lawres L, Plummer M, Virji AZ, Abraham A, Toh JY, Zandt MV, Aly ASI, Voelker DR, Mamoun CB. The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation. Scientific Reports 2017, 7: 14234. PMID: 29079738, PMCID: PMC5660193, DOI: 10.1038/s41598-017-14074-9.Peer-Reviewed Original ResearchConceptsMode of actionBlood stage developmentPantothenate kinase activityYeast mutantsMass spectrometry analysisBlood-stage parasitesPA-dependent mannerKinase activityPantothenate phosphorylationCAB1Pantothenate kinaseStage parasitesYeast growthCoenzyme ABiochemical analysisBlood stagesDirect competitionPantothenic acidSpectrometry analysisResistant P. falciparum strainsPhosphorylationStage developmentPlasmodium falciparumCompetitive inhibitorP. berghei
2014
Plasmodium yoelii Vitamin B5 Pantothenate Transporter Candidate is Essential for Parasite Transmission to the Mosquito
Hart RJ, Lawres L, Fritzen E, Mamoun C, Aly AS. Plasmodium yoelii Vitamin B5 Pantothenate Transporter Candidate is Essential for Parasite Transmission to the Mosquito. Scientific Reports 2014, 4: 5665. PMID: 25012929, PMCID: PMC4092334, DOI: 10.1038/srep05665.Peer-Reviewed Original ResearchConceptsSexual blood stage developmentYeast cellsLife cycle stagesNon-photosynthetic cellsParasite plasma membraneMultiple parasite life cycle stagesParasite life cycle stagesBlood stage developmentPantothenate transportGene-targeting techniquesHuman malaria parasiteCycle stagesFunctional complementationPAT inhibitorsPlasma membraneSporozoite formationTransporter candidatesVivo functionOocyst stageP. falciparuminParasite transmissionPantothenate concentrationPantothenate uptakeCoenzyme AMalaria parasites
2002
Mutations in the midway Gene Disrupt a Drosophila Acyl Coenzyme A: Diacylglycerol Acyltransferase
Buszczak M, Lu X, Segraves WA, Chang TY, Cooley L. Mutations in the midway Gene Disrupt a Drosophila Acyl Coenzyme A: Diacylglycerol Acyltransferase. Genetics 2002, 160: 1511-1518. PMID: 11973306, PMCID: PMC1462074, DOI: 10.1093/genetics/160.4.1511.Peer-Reviewed Original ResearchConceptsEgg chambersDiacylglycerol acyltransferaseNurse cellsAcyl coenzyme AMutant egg chambersNurse cell deathCell deathInsect cells resultsEgg chamber developmentCoenzyme AGermline apoptosisDrosophila oogenesisCytoplasm transportDGAT activityCells resultsChamber developmentNeutral lipidsGenesLipid metabolismDiacylglycerolApoptosisAcyltransferaseDrosophilaCellsOogenesis
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