2020
TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS
Cunningham K, Maulding K, Ruan K, Senturk M, Grima J, Sung H, Zuo Z, Song H, Gao J, Dubey S, Rothstein J, Zhang K, Bellen H, Lloyd T. TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS. ELife 2020, 9: e59419. PMID: 33300868, PMCID: PMC7758070, DOI: 10.7554/elife.59419.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAmyotrophic Lateral SclerosisAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBlotting, WesternC9orf72 ProteinDisease Models, AnimalDrosophila melanogasterFemaleFluorescent Antibody TechniqueFrontotemporal DementiaHeLa CellsHumansLysosomesMaleMicrophthalmia-Associated Transcription FactorMicroscopy, Electron, TransmissionMotor CortexConceptsNucleocytoplasmic transportNuclear importC9-ALS/FTDKey transcriptional regulatorAutophagic cargo degradationNeurodegenerative disease pathogenesisLysosome-like organellesProteostasis defectsGGGGCC hexanucleotide repeat expansionTranscriptional regulatorsCargo degradationKey regulatorUbiquitinated aggregatesCytoplasmic mislocalizationHuman cellsAmyotrophic lateral sclerosisGGGGCC repeatsHexanucleotide repeat expansionRepeat expansionFrontotemporal dementiaTFEBC9-ALSAutophagyRegulatorPotent suppressorNovel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue
Li X, Yang L, Mao Z, Pan X, Zhao Y, Gu X, Eckel‐Mahan K, Zuo Z, Tong Q, Hartig S, Cheng X, Du G, Moore D, Bellen H, Sesaki H, Sun K. Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue. The FASEB Journal 2020, 34: 8265-8282. PMID: 32294302, PMCID: PMC7336545, DOI: 10.1096/fj.201903100rr.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumFlx/Function of Drp1Multicellular organismsPeroxisomal fissionDrp1 ablationER retentionLD dynamicsAutophagy functionER functionNovel roleDrp1LD morphologyKnockout modelsProtein 1Unilocular morphologyAdipose tissueLipid metabolismDynaminOrganellesCold exposureTissueOrganismsLarge sizeMultilocular structure
2019
Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification
Şentürk M, Lin G, Zuo Z, Mao D, Watson E, Mikos A, Bellen H. Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification. Nature Cell Biology 2019, 21: 384-396. PMID: 30804504, PMCID: PMC6534127, DOI: 10.1038/s41556-019-0281-x.Peer-Reviewed Original ResearchMeSH KeywordsAmyotrophic Lateral SclerosisAnimalsAnimals, Genetically ModifiedAutophagyCarrier ProteinsCell Cycle ProteinsDrosophila melanogasterDrosophila ProteinsGene Expression Regulation, DevelopmentalHEK293 CellsHumansHydrogen-Ion ConcentrationLysosomesMutationNervous SystemSignal TransductionTOR Serine-Threonine KinasesConceptsAutophagic fluxDefective autophagic fluxEndoplasmic reticulum stressReticulum stressRegulator of autophagyConserved roleAmyotrophic lateral sclerosisMammalian cellsProteasomal degradationImpaired proteostasisDemise of neuronsUbiquilinLysosome acidificationFamilial amyotrophic lateral sclerosisLysosomal acidificationATPase activityMTORMutantsAutophagyDrosophilaProteostasisAcidificationCommon featureGenesLateral sclerosisVAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway
Mao D, Lin G, Tepe B, Zuo Z, Tan K, Senturk M, Zhang S, Arenkiel B, Sardiello M, Bellen H. VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway. Autophagy 2019, 15: 1214-1233. PMID: 30741620, PMCID: PMC6613884, DOI: 10.1080/15548627.2019.1580103.Peer-Reviewed Original ResearchAnimalsAutophagosomesAutophagyCarrier ProteinsDrosophilaDrosophila ProteinsEIF-2 KinaseEndoplasmic ReticulumEndosomesGolgi ApparatusHEK293 CellsHeLa CellsHumansLysosomal-Associated Membrane Protein 2LysosomesMembrane ProteinsMiceMice, Inbred C57BLMutationPhosphatidylinositol PhosphatesR-SNARE ProteinsRab GTP-Binding ProteinsRab7 GTP-Binding ProteinsVesicular Transport Proteins
2016
WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes
David-Morrison G, Xu Z, Rui Y, Charng W, Jaiswal M, Yamamoto S, Xiong B, Zhang K, Sandoval H, Duraine L, Zuo Z, Zhang S, Bellen H. WAC Regulates mTOR Activity by Acting as an Adaptor for the TTT and Pontin/Reptin Complexes. Developmental Cell 2016, 36: 139-151. PMID: 26812014, PMCID: PMC4730548, DOI: 10.1016/j.devcel.2015.12.019.Peer-Reviewed Original ResearchConceptsPontin/Reptin complexMTOR activityRapamycin complex 1Energy statusRegulation of metabolismEnergy-dependent activationDrosophila screenEnergy-dependent mannerTTT complexRAG interactionsMTORC1 activityMechanistic targetReptinPhysical interactionRegulatorDimerizationNeuronal dysfunctionComplexesPontinHomologActivationComplexes 1AdaptorAutophagyMTOR