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 ResearchConceptsProtein 1 light chain 3BLarge lipid dropletsLight chain 3BStarvation triggersLipidation reactionNoncanonical autophagyLysosomal pathwayAutophagic processStore lipidsAutophagy mechanismLipid dropletsATG3Large LDsProlonged starvationHuman liver cellsLC3BTimes of scarcityStarvationLiver cellsMacrolipophagyAutophagicClose proximityAutophagyATG5Microtubules
2021
TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis
Huang D, Xu B, Liu L, Wu L, Zhu Y, Ghanbarpour A, Wang Y, Chen FJ, Lyu J, Hu Y, Kang Y, Zhou W, Wang X, Ding W, Li X, Jiang Z, Chen J, Zhang X, Zhou H, Li JZ, Guo C, Zheng W, Zhang X, Li P, Melia T, Reinisch K, Chen XW. TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis. Cell Metabolism 2021, 33: 1655-1670.e8. PMID: 34015269, DOI: 10.1016/j.cmet.2021.05.006.Peer-Reviewed Original Research
2019
Distinct 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
2007
Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins
Shen J, Tareste DC, Paumet F, Rothman JE, Melia TJ. Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins. Cell 2007, 128: 183-195. PMID: 17218264, DOI: 10.1016/j.cell.2006.12.016.Peer-Reviewed Original ResearchConceptsSec1/Munc18 (SM) proteinsMunc18 proteinsSm proteinsIntracellular membrane fusionSNARE fusion machineryCognate SNAREsV-SNAREFusion specificityFusion machineryMunc18-1Membrane fusionMolecular mechanismsStimulatory subunitProteinNeurotransmitter releaseFundamental roleSNAREpinsSelective activationExocytosisSubunitsMachinerySnareFusionActivationBilayers