2023
Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis
Shi X, DeCiucis M, Grabinska K, Kanyo J, Liu A, Lam T, Shen H. Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. Molecular Cell 2023, 84: 802-810.e6. PMID: 38157846, PMCID: PMC10922821, DOI: 10.1016/j.molcel.2023.12.008.Peer-Reviewed Original ResearchProtein quality controlMitochondrial protein quality controlDual regulationMetabolic compartmentalizationIron homeostasisMitochondrial iron-sulfur clustersIron-sulfur clustersMitochondrial transportersProtein regulationMammalian cellsCRISPR knockoutCysteine residuesTransporter regulationLoop 1SLC25A39Glutathione homeostasisMetabolic sensingGlutathione uptakeMature neuronsProtein levelsHomeostasisRegulationAFG3L2Biochemical featuresMitochondrial glutathione levelsTNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes
Boutagy N, Fowler J, Grabinska K, Cardone R, Sun Q, Vazquez K, Whalen M, Zhu X, Chakraborty R, Martin K, Simons M, Romanoski C, Kibbey R, Sessa W. TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2218150120. PMID: 37695914, PMCID: PMC10515159, DOI: 10.1073/pnas.2218150120.Peer-Reviewed Original ResearchConceptsPyruvate dehydrogenase kinase 4Dehydrogenase kinase 4Lon proteasePyruvate dehydrogenase activityHistone acetylationMitochondrial metabolismKinase 4Specific gene lociPDH fluxEndothelial cellsSiRNA-mediated knockdownAcetyl-CoA generationLysine 27Gene transcriptionTCA fluxRNA sequencingHuman umbilical vein endothelial cellsProtein degradationHistone 3Gene locusUmbilical vein endothelial cellsNF-κB-dependent mechanismTricarboxylic acid cycle fluxVein endothelial cellsActive subunit
2021
De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus
Galosi S, Edani BH, Martinelli S, Hansikova H, Eklund EA, Caputi C, Masuelli L, Corsten-Janssen N, Srour M, Oegema R, Bosch DGM, Ellis CA, Amlie-Wolf L, Accogli A, Atallah I, Averdunk L, Barañano KW, Bei R, Bagnasco I, Brusco A, Demarest S, Alaix AS, Di Bonaventura C, Distelmaier F, Elmslie F, Gan-Or Z, Good JM, Gripp K, Kamsteeg EJ, Macnamara E, Marcelis C, Mercier N, Peeden J, Pizzi S, Pannone L, Shinawi M, Toro C, Verbeek NE, Venkateswaran S, Wheeler PG, Zdrazilova L, Zhang R, Zorzi G, Guerrini R, Sessa WC, Lefeber DJ, Tartaglia M, Hamdan FF, Grabińska KA, Leuzzi V. De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus. Brain 2021, 145: 208-223. PMID: 34382076, PMCID: PMC8967098, DOI: 10.1093/brain/awab299.Peer-Reviewed Original ResearchConceptsRetinitis pigmentosaNeurodegenerative disordersMovement disordersDe novo pathogenic variantsHypokinetic movement disordersCongenital disorderLong-term outcomesNeurodevelopmental disordersNovo pathogenic variantsNeuronal ceroid lipofuscinosisProgressive myoclonus epilepsyDisease courseNeurological declineClinical featuresProgressive encephalopathyPsychiatric disturbancesMyelinated fibersLarge cohortCortical tremorCognitive deteriorationDisease-causing variantsEndosomal-lysosomal pathwayAutosomal recessive formPathogenic variantsAltered lysosomesProgressive myoclonus epilepsies—Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes
Courage C, Oliver KL, Park EJ, Cameron JM, Grabińska KA, Muona M, Canafoglia L, Gambardella A, Said E, Afawi Z, Baykan B, Brandt C, di Bonaventura C, Chew HB, Criscuolo C, Dibbens LM, Castellotti B, Riguzzi P, Labate A, Filla A, Giallonardo AT, Berecki G, Jackson CB, Joensuu T, Damiano JA, Kivity S, Korczyn A, Palotie A, Striano P, Uccellini D, Giuliano L, Andermann E, Scheffer IE, Michelucci R, Bahlo M, Franceschetti S, Sessa WC, Berkovic SF, Lehesjoki AE. Progressive myoclonus epilepsies—Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes. American Journal Of Human Genetics 2021, 108: 722-738. PMID: 33798445, PMCID: PMC8059372, DOI: 10.1016/j.ajhg.2021.03.013.Peer-Reviewed Original ResearchConceptsPME genesProgressive myoclonus epilepsyWhole-exome sequencingPrevious genetic analysisGroup of genesVariety of proteinsPrevious disease associationsUnrelated individualsCopy number changesProtein glycosylationPathway genesEndosomal functionGenetic analysisDisease-causing variantsGenesLikely disease-causing variantsAdditional family membersGenetic heterogeneityHeterogeneous rare diseasesUnsolved casesDisease associationsNovel causeMyoclonus epilepsyHeterozygous variantsHomozygous variant
2020
Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation
Edani BH, Grabińska KA, Zhang R, Park EJ, Siciliano B, Surmacz L, Ha Y, Sessa WC. Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20794-20802. PMID: 32817466, PMCID: PMC7456142, DOI: 10.1073/pnas.2008381117.Peer-Reviewed Original ResearchConceptsActive site tunnelProtein glycosylationAtomic resolution structuresGlycosyl carrier lipidsΑ3 helixEnzyme active sitePTase activityResolution structureActive siteEndoplasmic reticulumHomodimeric formCarrier lipidRate-limiting stepGlycosylationCrystal structureDHDDSStructural elucidationPTaseIsoprene chainPrenyltransferaseUnique insightsComplexesUnfavorable stateNgBRHomodimericEndothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling
Zhou H, Mehta S, Srivastava SP, Grabinska K, Zhang X, Wong C, Hedayat A, Perrotta P, Fernández-Hernando C, Sessa WC, Goodwin JE. Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling. JCI Insight 2020, 5: e131384. PMID: 32051336, PMCID: PMC7098785, DOI: 10.1172/jci.insight.131384.Peer-Reviewed Original ResearchConceptsEndothelial glucocorticoid receptorVascular inflammationGlucocorticoid receptorGlucocorticoid receptor regulationGlucocorticoid receptor resultsUpregulation of WntEndogenous glucocorticoidsExogenous glucocorticoidsGlucocorticoid response elementCardiovascular diseaseMouse endothelial cellsMouse modelEndothelial WNTInflammationReceptor regulationEndothelial cellsReceptors resultsNext-generation sequencingReceptor interactionReceptorsRegulation of WntWnt pathwayGlucocorticoidsRecent dataWnt
2017
Long-Chain Polyprenols Promote Spore Wall Formation in Saccharomyces cerevisiae
Hoffmann R, Grabińska K, Guan Z, Sessa WC, Neiman AM. Long-Chain Polyprenols Promote Spore Wall Formation in Saccharomyces cerevisiae. Genetics 2017, 207: 1371-1386. PMID: 28978675, PMCID: PMC5714454, DOI: 10.1534/genetics.117.300322.Peer-Reviewed Original ResearchConceptsLong-chain polyprenolsSpore wallSynthesis of chitinSpore wall layerHaploid genomeCellular processesProtein glycosylationPrenyltransferase activitySporulating cellsWall formationDityrosine layerIsoprenoid lipidsChitin synthaseEndoplasmic reticulumVegetative cellsSRT1Lipid dropletsDividing cellsEssential precursorPrimary enzymeImportant functionsSaccharomycesPolyprenolsDolicholSugar carrierA conserved C-terminal RXG motif in the NgBR subunit of cis-prenyltransferase is critical for prenyltransferase activity
Grabińska KA, Edani BH, Park EJ, Kraehling JR, Sessa WC. A conserved C-terminal RXG motif in the NgBR subunit of cis-prenyltransferase is critical for prenyltransferase activity. Journal Of Biological Chemistry 2017, 292: 17351-17361. PMID: 28842490, PMCID: PMC5655512, DOI: 10.1074/jbc.m117.806034.Peer-Reviewed Original ResearchConceptsUndecaprenyl diphosphate synthaseDiphosphate synthaseDomains of lifeProtein glycosylation reactionsStrong conservationCellular functionsG motifTerminal tailPrenyltransferase activityFirst enzymeCis-prenyltransferaseBacterial enzymesIsoprene unitsSubunitsLarge familyNgBREnzyme activityG sequencesEnzymeDolichyl phosphateMotifSynthaseEukaryotesOrthologsArchaea
2016
cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases*
Grabińska K, Park EJ, Sessa WC. cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases*. Journal Of Biological Chemistry 2016, 291: 18582-18590. PMID: 27402831, PMCID: PMC5000101, DOI: 10.1074/jbc.r116.739490.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsUndecaprenyl diphosphate synthaseIsopentenyl diphosphateDomains of lifeConsecutive condensation reactionsPlant orthologsHeteromeric enzymeCis-PrenyltransferasesDiphosphate synthaseProtein glycosylationPolyprenyl diphosphateBacterial enzymesHuman diseasesMode of actionLarge familyOrthologsEnzymeRubber synthesisSubunitsNew insightsCarbon skeletonStructural componentsDiphosphateMammalsFungalGlycosylationNgBR is essential for endothelial cell glycosylation and vascular development
Park EJ, Grabińska K, Guan Z, Sessa WC. NgBR is essential for endothelial cell glycosylation and vascular development. EMBO Reports 2016, 17: 167-177. PMID: 26755743, PMCID: PMC5290814, DOI: 10.15252/embr.201540789.Peer-Reviewed Original ResearchConceptsVascular developmentCis-prenyltransferase activityEmbryonic lethalityKnockout embryosProtein glycosylationTransmembrane proteinDefective glycosylationCell glycosylationEndothelial cellsDevelopment defectsKnockout resultsNgBRDolichol phosphateVE-cadherinGlycosylationYolk sacProteinEndothelial proteinsCellsIntegrated roleEmbryogenesisSubunitsEmbryosApoptosisEnd products
2014
Mutation of Nogo-B Receptor, a Subunit of cis-Prenyltransferase, Causes a Congenital Disorder of Glycosylation
Park EJ, Grabińska K, Guan Z, Stránecký V, Hartmannová H, Hodaňová K, Barešová V, Sovová J, Jozsef L, Ondrušková N, Hansíková H, Honzík T, Zeman J, Hůlková H, Wen R, Kmoch S, Sessa WC. Mutation of Nogo-B Receptor, a Subunit of cis-Prenyltransferase, Causes a Congenital Disorder of Glycosylation. Cell Metabolism 2014, 20: 448-457. PMID: 25066056, PMCID: PMC4161961, DOI: 10.1016/j.cmet.2014.06.016.Peer-Reviewed Original ResearchConceptsProtein glycosylationCis-prenyltransferaseGPI anchor biosynthesisDolichol synthesisSynthesis of dolicholO-mannosylationAnchor biosynthesisFirst enzymeGenetic basisC-terminusCongenital disorderFunction mutationsGlycosylationEssential roleEnhanced accumulationMutationsYeastNgBRSubunitsDolicholFibroblastsBiosynthesisTerminusFree cholesterolProtein
2010
Molecular characterization of the cis-prenyltransferase of Giardia lamblia
Grabińska K, Cui J, Chatterjee A, Guan Z, Raetz C, Robbins P, Samuelson J. Molecular characterization of the cis-prenyltransferase of Giardia lamblia. Glycobiology 2010, 20: 824-832. PMID: 20308470, PMCID: PMC2900897, DOI: 10.1093/glycob/cwq036.Peer-Reviewed Original ResearchConceptsIsoprene unitsDouble deletion mutantGPI anchor synthesisMost eukaryotesHigher eukaryotesAnchor synthesisN-glycosylationGlycosylphosphatidylinositol (GPI) anchorCis-prenyltransferaseKinase activityPolyprenyl pyrophosphateBacterial enzymesDolichol kinase activityDolichol kinaseMolecular characterizationImportant enzymeN-glycansEukaryotesProtistsPolyprenol lipidsNormal growthPyrophosphate linkageEnzymeGiardia lambliaDolichol
2009
The YTA7 gene is involved in the regulation of the isoprenoid pathway in the yeast Saccharomyces cerevisiae
Kuranda K, Grabinska K, Berges T, Karst F, Leberre V, Sokol S, François J, Palamarczyk G. The YTA7 gene is involved in the regulation of the isoprenoid pathway in the yeast Saccharomyces cerevisiae. FEMS Yeast Research 2009, 9: 381-390. PMID: 19416104, DOI: 10.1111/j.1567-1364.2009.00485.x.Peer-Reviewed Original ResearchConceptsIsoprenoid pathwayFPP synthaseTwo-hybrid screenMembrane-associated proteinsBiosynthesis of hemeIsoprenoid biosynthesisProtein partnersPresence of lovastatinYeast SaccharomycesN-glycosylationSterol biosynthesisSqualene synthaseCis-prenyltransferaseEndoplasmic reticulumIsoprenoid compoundsZaragozic acidsBiosynthesisCellular levelGenesEnzymatic activityExpression levelsSaccharomycesPathwaySynthaseRegulation
2008
Dolichyl-Phosphate-Glucose Is Used To Make O-Glycans on Glycoproteins of Trichomonas vaginalis▿ †
Grabińska K, Ghosh S, Guan Z, Cui J, Raetz C, Robbins P, Samuelson J. Dolichyl-Phosphate-Glucose Is Used To Make O-Glycans on Glycoproteins of Trichomonas vaginalis▿ †. MSphere 2008, 7: 1344-1351. PMID: 18552282, PMCID: PMC2519777, DOI: 10.1128/ec.00061-08.Peer-Reviewed Original ResearchConceptsDol-P-Man synthase activityO-glycansSynthase activityNumerous gene duplicationsSaccharomyces cerevisiae membranesDolichyl-P-mannose synthaseN-glycosylation defectGene duplicationHuge genomeDPM1 geneNumerous genesGlycosylation defectsDolichyl-PPGene productsRecombinant proteinsSugar donorIsoprene unitsEndogenous glycoproteinsGenesDolichyl phosphateMembraneGlycoproteinFirst demonstrationProtistsALG5
2006
Prenylation of Saccharomyces cerevisiae Chs4p Affects Chitin Synthase III Activity and Chitin Chain Length▿
Grabińska K, Magnelli P, Robbins P. Prenylation of Saccharomyces cerevisiae Chs4p Affects Chitin Synthase III Activity and Chitin Chain Length▿. MSphere 2006, 6: 328-336. PMID: 17142567, PMCID: PMC1797950, DOI: 10.1128/ec.00203-06.Peer-Reviewed Original ResearchConceptsChitin synthase IIIChitin synthase III activityPlasma membrane associationC-terminal endMembrane associationCSIII activityChs4pCatalytic subunitProtein factorsChitin biosynthesisSynthase IIIFarnesyl transferaseYeast cellsPrenylationChitin polymersPrenyl moietyEnzymatic activityChitin contentAttachment sitesAverage chain lengthChs3pSaccharomycesVivoBiosynthesisFTase
2005
Rsp5 ubiquitin ligase affects isoprenoid pathway and cell wall organization in S. cerevisiae.
Kamińska J, Kwapisz M, Grabińska K, Orłowski J, Boguta M, Palamarczyk G, Zoładek T. Rsp5 ubiquitin ligase affects isoprenoid pathway and cell wall organization in S. cerevisiae. Acta Biochimica Polonica 2005, 52: 207-20. PMID: 15827618, DOI: 10.18388/abp.2005_3510.Peer-Reviewed Original ResearchConceptsCell wall integrityIsoprenoid pathwayWall integrityPlasma membraneRsp5 ubiquitin-protein ligaseCell wallCell wall organizationRsp5 ubiquitin ligaseUbiquitin-protein ligaseCell wall structureWild-type strainNorthern blot analysisWall organizationProtein glycosylationDimethylallyl diphosphateType strainUbiquitin ligaseIsopentenyl diphosphateS. cerevisiaeCytosolic distributionErgosterol biosynthesisKey enzymeRegulatory roleChitin levelsMolecular levelFunctional relationships between the Saccharomyces cerevisiae cis-prenyltransferases required for dolichol biosynthesis.
Grabińska K, Sosińska G, Orłowski J, Swiezewska E, Berges T, Karst F, Palamarczyk G. Functional relationships between the Saccharomyces cerevisiae cis-prenyltransferases required for dolichol biosynthesis. Acta Biochimica Polonica 2005, 52: 221-32. PMID: 15827619, DOI: 10.18388/abp.2005_3511.Peer-Reviewed Original ResearchConceptsEnzymatic activityCis-prenyltransferase activityLong-chain dolicholsYeast SaccharomycesShorter speciesRER2Dolichol biosynthesisLevels of mRNADiphosphate formationIsoprene unitsSRT1SaccharomycesOverexpressionDolichol contentGenesPreferential synthesisProteinFunctional relationshipMRNADPM1TranscriptionBiosynthesisFarnesylSpecies
2002
Dolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight into the regulatory role of farnesyl diphosphate synthase
Grabińska K, Palamarczyk G. Dolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight into the regulatory role of farnesyl diphosphate synthase. FEMS Yeast Research 2002, 2: 259-265. DOI: 10.1111/j.1567-1364.2002.tb00093.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDolichol biosynthesisMevalonate pathwayYeast Saccharomyces cerevisiaeTranscription of genesAAA ATPase familyNon-sterol derivativesEffects of overexpressionATPase familyNon-sterol compoundsProtein glycosylationSaccharomyces cerevisiaeFirst enzymeIsoprenoid lipidsRegulatory enzymeRegulatory roleEffects of FPPBiosynthesisFarnesylCoA reductaseMevalonic acidPathwayEnzymeSynthaseFPPPresent reviewDolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight into the regulatory role of farnesyl diphosphate synthase
Grabińska K, Palamarczyk G. Dolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight into the regulatory role of farnesyl diphosphate synthase. FEMS Yeast Research 2002, 2: 259-265. PMID: 12702274, DOI: 10.1016/s1567-1356(02)00110-1.Peer-Reviewed Original ResearchConceptsFarnesyl diphosphateDolichol biosynthesisMevalonate pathwayOverexpression of farnesyl diphosphate synthaseYeast Saccharomyces cerevisiaeAAA ATPase familyFarnesyl diphosphate synthaseDerivatives of mevalonic acidDiphosphate synthaseProtein glycosylationATPase familyIsoprenoid lipidsRegulatory enzymeMevalonic acidMevalonateRegulatory roleBiosynthesisDolicholYeastPathwayProteinEnzymeYta7FarnesylationTranscriptionThe isoprenoid biosynthetic pathway in Saccharomyces cerevisiae is affected in a maf1-1 mutant with altered tRNA synthesis
Kamińska J, Grabińska K, Kwapisz M, Sikora J, Smagowicz W, Palamarczyk G, Żołądek T, Boguta M. The isoprenoid biosynthetic pathway in Saccharomyces cerevisiae is affected in a maf1-1 mutant with altered tRNA synthesis. FEMS Yeast Research 2002, 2: 31-37. DOI: 10.1016/s1567-1356(01)00059-9.Peer-Reviewed Original ResearchIsoprenoid pathwayIsoprenoid biosynthetic pathwayCellular tRNA levelsTRNA synthesisTRNA biosynthesisTRNA levelsSaccharomyces cerevisiaeBiosynthetic pathwayComplex regulationIsopentenyltransferaseProtein levelsMutantsErgosterol contentBiosynthesisPathwayIsopentenylationCerevisiaeSaccharomycesYeastTranscriptsRegulationExpressionDirect effectCells