Please use this identifier to cite or link to this item: https://doi.org/10.1080/15548627.2021.1896157
DC FieldValue
dc.titleThe BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore
dc.contributor.authorHao-Chun Chang
dc.contributor.authorRan N. Tao
dc.contributor.authorChong Teik Tan
dc.contributor.authorYa jun Wu
dc.contributor.authorBoon Huat Bay
dc.contributor.authorVictor C. Yu
dc.date.accessioned2021-12-17T01:14:54Z
dc.date.available2021-12-17T01:14:54Z
dc.date.issued2021-03-30
dc.identifier.citationHao-Chun Chang, Ran N. Tao, Chong Teik Tan, Ya jun Wu, Boon Huat Bay, Victor C. Yu (2021-03-30). The BAX-binding protein MOAP1 associates with LC3 and promotes closure of the phagophore. Autophagy 17 (11) : 3725-3739. ScholarBank@NUS Repository. https://doi.org/10.1080/15548627.2021.1896157
dc.identifier.issn1554-8627
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/210948
dc.description.abstractMOAP1 (modulator of apoptosis 1) is a BAX-binding protein tightly regulated by the ubiquitin-proteasome system. Apoptotic stimuli stabilize MOAP1 protein and facilitate its interaction with BAX to promote apoptosis. Here we show that in contrast to being resistant to apoptotic stimuli, MOAP1-deficient cells are hypersensitive to cell death mediated by starvation rendered by EBSS treatment. MOAP1-deficient cells exhibited impairment in macroautophagy/autophagy signaling induced by EBSS. Mechanistic analysis revealed that MOAP1-deficient cells had no notable defect in the recruitment of the pre-autophagosomal phosphatidylinositol-3-phosphate (PtdIns3P)-binding proteins, ZFYVE1/DFCP1 and WIPI2, nor in the LC3 lipidation mechanism regulated by the ATG12–ATG5-ATG16L1 complex upon EBSS treatment. Interestingly, MOAP1 is required for facilitating efficient closure of phagophore in the EBSS-treated cells. Analysis of LC3-positive membrane structures using Halo-tagged LC3 autophagosome completion assay showed that predominantly unclosed phagophore rather than closed autophagosome was present in the EBSS-treated MOAP1-deficient cells. The autophagy substrate SQSTM1/p62, which is normally contained within the enclosed autophagosome under EBSS condition, was also highly sensitive to degradation by proteinase K in the absence of MOAP1. MOAP1 binds LC3 and the binding is critically dependent on a LC3-interacting region (LIR) motif detected at its N-terminal region. Re-expression of MOAP1, but not its LC3-binding defective mutant, MOAP1-LIR, in the MOAP1-deficient cells, restored EBSS-induced autophagy. Together, these observations suggest that MOAP1 serves a distinct role in facilitating autophagy through interacting with LC3 to promote efficient phagophore closure during starvation. Abbreviations: CQ: Chloroquine; EBSS: Earle’s Balanced Salt Solution; GABARAP: Gamma-Amino Butyric Acid Receptor Associated Protein; IF: Immunofluorescence; IP: Immunoprecipitation; LAMP1: Lysosomal-Associated Membrane Protein 1; LIR: LC3-Interacting Region; MAP1LC3/LC3: Microtubule Associated Protein 1 Light Chain 3; MEF: Mouse Embryonic Fibroblast; MOAP1: Modulator of Apoptosis 1; PE: Phosphatidylethanolamine; PtdIns3K: class III PtdIns3K complex I; PtdIns3P: Phosphatidylinositol-3-phosphate; STX17: Syntaxin 17; ULK1: unc-51 like autophagy activating kinase 1.
dc.publisherTaylor & Francis
dc.sourceTaylor & Francis
dc.subjectAutophagosome formation
dc.subjectautophagy
dc.subjectcell death
dc.subjectLC3-binding protein
dc.subjectLIR motif
dc.subjectnutrient deprivation
dc.typeArticle
dc.contributor.departmentDEPT OF PHARMACY
dc.contributor.departmentDEPT OF ANATOMY
dc.description.doi10.1080/15548627.2021.1896157
dc.description.sourcetitleAutophagy
dc.description.volume17
dc.description.issue11
dc.description.page3725-3739
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10.108015548627.2021.1896157.zip290.3 MBZIP

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.