Zhongyuan Zuo, MS
Senior Staff ScientistCards
About
Research
Publications
2024
Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Liao J, Chung H, Shih C, Wong K, Dutta D, Nil Z, Burns C, Kanca O, Park Y, Zuo Z, Marcogliese P, Sew K, Bellen H, Verheyen E. Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila. Nature Communications 2024, 15: 3326. PMID: 38637532, PMCID: PMC11026413, DOI: 10.1038/s41467-024-47623-8.Peer-Reviewed Original ResearchConceptsMitochondrial fissionRNA polymerase IINon-nuclear functionsDrp1-mediated fissionPhosphorylation of Drp1Elevated levels of ROSMitochondrial kinaseBang sensitivityLevels of PINK1Polymerase IIFly lifespanPhosphorylated Drp1PINK1 deficiencyDrp1 phosphorylationTranscriptional controlElongated mitochondriaLevels of ROSOverexpression of CDK8CDK8Drp1Mitochondrial dysmorphologyBehavioral defectsPINK1DrosophilaCytoplasm
2023
A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels
Dutta D, Kanca O, Byeon S, Marcogliese P, Zuo Z, Shridharan R, Park J, Lin G, Ge M, Heimer G, Kohler J, Wheeler M, Kaipparettu B, Pandey A, Bellen H. A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels. Nature Metabolism 2023, 5: 1595-1614. PMID: 37653044, PMCID: PMC11151872, DOI: 10.1038/s42255-023-00873-0.Peer-Reviewed Original ResearchConceptsFatty acid synthesisFe-S cluster biogenesisMitochondrial fatty acid synthesisCeramide levelsMost eukaryotic cellsElevated ceramide levelsIron metabolismCluster biogenesisEukaryotic cellsLoss of functionCellular lipidomeEnoyl coenzymeNeurodegenerative phenotypeIron homeostasisHuman-derived fibroblastsMechanistic linkAcid synthesisCeramideMECRMetabolismNeurodegenerationMtFASBiogenesisLast stepMitochondriaDaam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury
Wang C, Zuo Z, Jo J, Kim K, Madamba C, Ye Q, Jung S, Bellen H, Lee H. Daam2 phosphorylation by CK2α negatively regulates Wnt activity during white matter development and injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304112120. PMID: 37607236, PMCID: PMC10469030, DOI: 10.1073/pnas.2304112120.Peer-Reviewed Original ResearchConceptsOL developmentWhite matter injuryCentral nervous systemWnt/β-cateninWhite matter developmentWnt activityNeonatal hypoxiaBehavioral recoveryMyelin repairMyelin restorationNervous systemProtective roleOligodendrocyte developmentΒ-cateninWnt pathwayInjuryMyelinationBiological mechanismsNew biological mechanismsEarly differentiationPhosphorylationDemyelinationPathwayVery-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation
Chung H, Ye Q, Park Y, Zuo Z, Mok J, Kanca O, Tattikota S, Lu S, Perrimon N, Lee H, Bellen H. Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation. Cell Metabolism 2023, 35: 855-874.e5. PMID: 37084732, PMCID: PMC10160010, DOI: 10.1016/j.cmet.2023.03.022.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisAdministration of fingolimodFunctions of S1PNF-κB activationSphingosine-1-phosphate (S1P) synthesisS1P receptor antagonistsElevated VLCFAAutoimmune encephalomyelitisFatty acidsMacrophage infiltrationReceptor antagonistImmune cellsMouse modelTreatment avenuesVLCFA levelsFly gliaLong-chain fatty acidsGliaS1P pathwayS1PNeuroinflammationFingolimodVLCFAAbundant fatty acidsExploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14)
Lin G, Tepe B, McGrane G, Tipon R, Croft G, Panwala L, Hope A, Liang A, Zuo Z, Byeon S, Wang L, Pandey A, Bellen H. Exploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14). ELife 2023, 12: e82555. PMID: 36645408, PMCID: PMC9889087, DOI: 10.7554/elife.82555.Peer-Reviewed Original ResearchConceptsPatient-derived neural progenitor cellsNeural progenitor cellsPatient-derived neuronsPediatric neurodegenerative disorderRetromer functionMitochondrial morphologyEndolysosomal pathwayMitochondrial defectsProlong lifespanNeurodegenerative phenotypeProgenitor cellsMouse modelRecessive variantsNeurodegenerative disordersGene therapy approachesPathwayInfantile neuroaxonal dystrophyHomologCellsTherapeutic strategiesAzoramidePurkinje cellsFliesPhenotypeMetabolism
2022
Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila
Bosch J, Ugur B, Pichardo-Casas I, Rabasco J, Escobedo F, Zuo Z, Brown B, Celniker S, Sinclair D, Bellen H, Perrimon N. Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila. ELife 2022, 11: e82709. PMID: 36346220, PMCID: PMC9681215, DOI: 10.7554/elife.82709.Peer-Reviewed Original ResearchConceptsSmall open reading framesClasses of genesShares sequence similarityOpen reading frameSequence similarityBicistronic transcriptBiological functionsPhenotypic analysisMitochondrial functionImportant regulatorThousands of peptidesNeuronal functionGenesWealth of informationTranscriptsAnimal lethalityPeptidesRecent studiesParalogsDrosophilaSmORFsMitochondriaRegulatorRegulatesNeuronal peptidesNeuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia
Wang L, Lin G, Zuo Z, Li Y, Byeon S, Pandey A, Bellen H. Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia. Science Advances 2022, 8: eabn3326. PMID: 35857503, PMCID: PMC9278864, DOI: 10.1126/sciadv.abn3326.Peer-Reviewed Original ResearchAn expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination
Kanca O, Zirin J, Hu Y, Tepe B, Dutta D, Lin W, Ma L, Ge M, Zuo Z, Liu L, Levis R, Perrimon N, Bellen H. An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination. ELife 2022, 11: e76077. PMID: 35723254, PMCID: PMC9239680, DOI: 10.7554/elife.76077.Peer-Reviewed Original ResearchLow doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies
Martelli F, Hernandes N, Zuo Z, Wang J, Wong C, Karagas N, Roessner U, Rupasinghe T, Robin C, Venkatachalam K, Perry T, Batterham P, Bellen H. Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies. ELife 2022, 11: e73812. PMID: 35191376, PMCID: PMC8863376, DOI: 10.7554/elife.73812.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesBeneficial insectsBeneficial insect speciesElevated reactive oxygen speciesInsect speciesInsect pestsMitochondrial stressMitochondrial defectsAdult virgin femalesLysosomal defectsGlobal declineAntioxidant N-acetylcysteine amidePopulation sizeSpinosad toxicityMode of actionLipid storageMetabolic tissuesVirgin femalesInsecticide applicationsLysosomal dysfunctionInsectsSevere neurodegenerationSynthetic insecticidesOxygen speciesAlpha 6Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin
Cristobal C, Wang C, Zuo Z, Smith J, Lindeke-Myers A, Bellen H, Lee H. Daam2 Regulates Myelin Structure and the Oligodendrocyte Actin Cytoskeleton through Rac1 and Gelsolin. Journal Of Neuroscience 2022, 42: 1679-1691. PMID: 35101966, PMCID: PMC8896627, DOI: 10.1523/jneurosci.1517-21.2022.Peer-Reviewed Original ResearchConceptsGelsolin levelsOL differentiationMyelin sheathCNS functionMorphogenesis 2Motor coordination deficitsActin cytoskeletonWhite matter diseaseMyelin structureConditional knockout miceWhite matter developmentMyelin compactionMyelin decompactionNeuronal healthCKO miceCoordination deficitsFunctional myelinCompact myelin sheathKnockout miceWhite matterPostnatal developmentProper myelin formationOligodendrocytesMyelin formationOL cultures
Links
Media
Whole cell model was generated with Apeer and reconstructed with Arivis Vision 4D.