2023
LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy
Omrane M, Ben M'Barek K, Santinho A, Nguyen N, Nag S, Melia T, Thiam A. LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy. Developmental Cell 2023, 58: 1266-1281.e7. PMID: 37315562, PMCID: PMC10686041, DOI: 10.1016/j.devcel.2023.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagosomesAutophagyAutophagy-Related Protein 5HumansLipid DropletsMiceMicrotubule-Associated ProteinsConceptsProtein 1 light chain 3BLarge lipid dropletsLight chain 3BStarvation triggersLipidation reactionNoncanonical autophagyLysosomal pathwayAutophagic processStore lipidsAutophagy mechanismLipid dropletsATG3Large LDsProlonged starvationHuman liver cellsLC3BTimes of scarcityStarvationLiver cellsMacrolipophagyAutophagicClose proximityAutophagyATG5Microtubules
2019
Maturation 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
2018
Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases
Kauffman KJ, Yu S, Jin J, Mugo B, Nguyen N, O'Brien A, Nag S, Lystad AH, Melia TJ. Delipidation of mammalian Atg8-family proteins by each of the four ATG4 proteases. Autophagy 2018, 14: 992-1010. PMID: 29458288, PMCID: PMC6103404, DOI: 10.1080/15548627.2018.1437341.Peer-Reviewed Original ResearchConceptsAtg8-family proteinsAtg4 proteasesATG8 proteinsMammalian Atg8 proteinsMacroautophagy/autophagySimilar enzymatic activityProteolytic processing eventsLIR motifATG4 familyProcessing eventsPhysical anchoringProteinEnzymatic activityProteaseSoluble substratesATG4BTerminal glycinePhagophoreHomologLipidsDelipidationAutophagosomesAutophagyMotifSubstrate
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
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