2023
LC3 conjugation to lipid droplets
Omrane M, Melia T, Thiam A. LC3 conjugation to lipid droplets. Autophagy 2023, 19: 3251-3253. PMID: 37599471, PMCID: PMC10621252, DOI: 10.1080/15548627.2023.2249390.Peer-Reviewed Original ResearchMeSH KeywordsAutophagosomesAutophagyAutophagy-Related Protein 8 FamilyAutophagy-Related ProteinsLipid DropletsConceptsLipid dropletsResponse to different signalsDegradation of lipid dropletsUbiquitin-conjugating enzymeLong-term-starved cellsLC3-interacting regionArtificial lipid dropletsPatatin-like phospholipase domainMicrotubule-associated protein 1 light chain 3 betaFYVE domainTethering factorsE2 enzymesLIR motifLD surfaceZinc fingerEndoplasmic reticulumLipidated LC3BPerilipin 1Phospholipase domainAutophagosome formationAssembly platformPromote degradationProlonged starvationSequestosome 1ZFYVE1/DFCP1ATG9 vesicles comprise the seed membrane of mammalian autophagosomes
Olivas T, Wu Y, Yu S, Luan L, Choi P, Guinn E, Nag S, De Camilli P, Gupta K, Melia T. ATG9 vesicles comprise the seed membrane of mammalian autophagosomes. Journal Of Cell Biology 2023, 222: e202208088. PMID: 37115958, PMCID: PMC10148236, DOI: 10.1083/jcb.202208088.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagosomesAutophagyAutophagy-Related ProteinsLipidsMammalsMembrane ProteinsProtein TransportConceptsAtg9 vesiclesMammalian autophagosomesStyrene maleic acid lipid particlesLipid scramblase activityLC3-IIAutophagosomes formAutophagosome membraneMature autophagosomesScramblase activityAutophagosome formationAtg9Lipid transportMembrane growthAutophagosomesNanoscale organizationProtein-mediated transferProteinMembrane surface areaOrganellesVesiclesSeed membraneMembraneLipid particlesLipidsDifferent stages
2021
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Chandra S, Mannino PJ, Thaller DJ, Ader NR, King MC, Melia TJ, Lusk CP. Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome. Journal Of Cell Biology 2021, 220: e202103030. PMID: 34714326, PMCID: PMC8575018, DOI: 10.1083/jcb.202103030.Peer-Reviewed Original ResearchMeSH KeywordsAutophagosomesAutophagyAutophagy-Related ProteinsCytoplasmic VesiclesGreen Fluorescent ProteinsNuclear EnvelopeProtein DomainsReceptors, Cytoplasmic and NuclearSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStructure-Activity RelationshipTime FactorsVacuolesVesicular Transport ProteinsConceptsInner nuclear membraneNuclear envelope lumenOuter nuclear membraneNuclear membraneSplit-GFP reporterNuclear envelope localizationINM proteinsAutophagy apparatusEnvelope localizationLumenal vesiclesLumenal domainCargo adaptorsAtg39Sequence elementsCorrelative lightVesiclesAutophagosomesMembraneNucleophagyAdaptorReporterProteinOverexpressionMotifA model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis
Ghanbarpour A, Valverde DP, Melia TJ, Reinisch KM. A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2101562118. PMID: 33850023, PMCID: PMC8072408, DOI: 10.1073/pnas.2101562118.Peer-Reviewed Original ResearchConceptsLipid transfer proteinEndoplasmic reticulumAutophagy protein ATG2Membrane dynamics processesTransfer proteinOrganelle biogenesisAutophagosome biogenesisCytosolic leafletOrganelle membranesMembrane expansionScramblasesVMP1Lipid homeostasisTMEM41BAtg9BiogenesisBulk lipidsProteinLipidsAtg2GolgiOrganellesReticulumLeafletsHomeostasis
2019
ATG2 transports lipids to promote autophagosome biogenesis
Valverde DP, Yu S, Boggavarapu V, Kumar N, Lees JA, Walz T, Reinisch KM, Melia TJ. ATG2 transports lipids to promote autophagosome biogenesis. Journal Of Cell Biology 2019, 218: 1787-1798. PMID: 30952800, PMCID: PMC6548141, DOI: 10.1083/jcb.201811139.Peer-Reviewed Original ResearchMeSH KeywordsAutophagosomesAutophagyAutophagy-Related ProteinsBiological TransportCRISPR-Cas SystemsEndoplasmic ReticulumHEK293 CellsHumansLipidsVesicular Transport ProteinsConceptsProtein-mediated lipid transferLipid transferLipid transfer proteinTransfers lipidsAutophagosome biogenesisAutophagosome membraneDonor membranesN-terminal fragmentDifferent organellesAutophagy proteinsAutophagosome formationKO cellsContact sitesSpecific machineryLipid homeostasisClear functionAtg2BiogenesisProteinDelivery of lipidsLipidsATG2AMembraneOrganellesAutophagosomesMaturation and Clearance of Autophagosomes in Neurons Depends on a Specific Cysteine Protease Isoform, ATG-4.2
Hill SE, Kauffman KJ, Krout M, Richmond JE, Melia TJ, Colón-Ramos DA. Maturation and Clearance of Autophagosomes in Neurons Depends on a Specific Cysteine Protease Isoform, ATG-4.2. Developmental Cell 2019, 49: 251-266.e8. PMID: 30880001, PMCID: PMC6482087, DOI: 10.1016/j.devcel.2019.02.013.Peer-Reviewed Original ResearchConceptsGenetic screenForward genetic screenClearance of autophagosomesProtease isoformsAutophagosomesCell bodiesAutophagosome clearanceSynaptic materialNeurodegenerative diseasesMaturationRetrograde transportNeuronal activityAbnormal accumulationNeuronsSingle neuronsClearanceGABARAPVivoTraffickingAutophagyScreenIsoformsMechanismMembraneSynapseDistinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes
Lystad AH, Carlsson SR, de la Ballina LR, Kauffman KJ, Nag S, Yoshimori T, Melia TJ, Simonsen A. Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nature Cell Biology 2019, 21: 372-383. PMID: 30778222, PMCID: PMC7032593, DOI: 10.1038/s41556-019-0274-9.Peer-Reviewed Original ResearchConceptsMembrane-binding regionTerminal membrane-binding regionLC3B lipidationMembrane-binding amphipathic helixLC3/GABARAPDifferent cellular conditionsDouble-membrane phagophoreSingle-membrane structuresGABARAP proteinsCanonical autophagyCellular conditionsAmphipathic helixTarget membraneMembrane bindingC-terminusDistinct functionsCovalent modificationLipidationΒ isoformsEssential roleKey eventsIsoformsPhagophoreGABARAPMacroautophagy
2014
Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3
Nath S, Dancourt J, Shteyn V, Puente G, Fong WM, Nag S, Bewersdorf J, Yamamoto A, Antonny B, Melia TJ. Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3. Nature Cell Biology 2014, 16: 415-424. PMID: 24747438, PMCID: PMC4111135, DOI: 10.1038/ncb2940.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsAnimalsApoptosis Regulatory ProteinsAutophagy-Related Protein 7Autophagy-Related Protein 8 FamilyAutophagy-Related ProteinsCell MembraneCytoskeletal ProteinsHeLa CellsHumansHydrophobic and Hydrophilic InteractionsLiposomesMembrane ProteinsMiceMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsMutationPhosphatidylethanolaminesRatsSignal TransductionStress, PhysiologicalTransfectionUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesConceptsLipid-packing defectsLC3/GABARAP familyLC3/GABARAP lipidationAmino-terminal amphipathic helixE2-like enzymeGABARAP familyAutophagic machineryIsolation membraneAmphipathic helixIntracellular membranesAutophagy proteinsRescue experimentsATG3LipidationCurved rimProteinMotifPhysiologic roleMembranePhagophoreAutophagosomesMachineryHelixEnzyme
2012
The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation
Choy A, Dancourt J, Mugo B, O’Connor T, Isberg RR, Melia TJ, Roy CR. The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation. Science 2012, 338: 1072-1076. PMID: 23112293, PMCID: PMC3682818, DOI: 10.1126/science.1227026.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAutophagyAutophagy-Related Protein 7Autophagy-Related Protein 8 FamilyAutophagy-Related ProteinsBacterial ProteinsCell Culture TechniquesCysteine ProteasesGene DeletionGlycineHEK293 CellsHost-Pathogen InteractionsHumansHydrolysisLegionella pneumophilaLegionnaires' DiseaseMicrofilament ProteinsPhagosomesUbiquitin-Activating EnzymesUbiquitin-Conjugating EnzymesConceptsATG8 proteinsIntracellular pathogen Legionella pneumophilaPathogen Legionella pneumophilaAdjacent aromatic residuesCarboxyl-terminal glycine residueAutophagosome membraneEukaryotic cellsAutophagy pathwayGlycine residueAromatic residuesIntracellular pathogensRavZAutophagyProteinLegionella pneumophilaSpecific mechanismsResiduesPathogensATG3MicrobesAtg7CytosolVacuolesPathwayPneumophila
2011
SNARE Proteins Are Required for Macroautophagy
Nair U, Jotwani A, Geng J, Gammoh N, Richerson D, Yen WL, Griffith J, Nag S, Wang K, Moss T, Baba M, McNew JA, Jiang X, Reggiori F, Melia TJ, Klionsky DJ. SNARE Proteins Are Required for Macroautophagy. Cell 2011, 146: 290-302. PMID: 21784249, PMCID: PMC3143362, DOI: 10.1016/j.cell.2011.06.022.Peer-Reviewed Original ResearchConceptsAutophagosome biogenesisAutophagosome membrane expansionV-SNAREs Sec22Vacuole/lysosomeDouble-membrane autophagosomesT-SNAREsAtg9 transportSNARE proteinsDe novo formationAutophagy componentsFusion eventsMembrane expansionTubulovesicular clustersNovo formationAtg8BiogenesisMacroautophagyProteinPhysiological concentrationsSec22Atg9Ykt6Tlg2OrganellesAutophagosomes