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PXD028745

PXD028745 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAtg8ylation coordinates stress granule formation and mTOR inactivation in response to lysosomal damage
DescriptionStress granule formation is a part of cellular homeostatic responses, with prototypical inducers being viral infections, heat shock and oxidative damage. Here we show that lysosomal damage is a previously unappreciated robust inducer of stress granule formation interlinked with mTOR inactivation during lysosomal damage. We find the two processes to be coordinated by a non-autophagy function of mammalian Atg8 proteins (mAtg8s). Stress granules were induced in response to biochemical damage and diverse lysosome damaging biological agents including SARS-CoV-2 ORF3a, Mycobacterium tuberculosis and protopathic tau. Proteomic analyses of purified lysosomes subjected to biochemical damage revealed recruitment to lysosomes of a network of stress granule proteins, including G3BP1 and NUFIP2. G3BP1 and NUFIP2 contributed to inactivation of mTOR during lysosomal damage via the Ragulator-RagA/B system. Lysosomal damage recruited a subset of mAtg8s commonly related to autophagy but also known to associate with other stressed or remodeling membranes. The GABARAP subset of mAtg8s interacted with G3BP1 and NUFIP2 and were required for NUFIP2 and G3BP1 recruitment to the damaged lysosomes. GABARAPs acted as a switch between the utilization of G3BP1 and NUFIP2 in stress granule formation vs. their role in mTOR inactivation. We furthermore found that mAtg8s lipidation, referred herein as Atg8ylation to distinguish it from its conventional implication in autophagy, but not the canonical autophagy factors ATG13, FIP200, and ATG9A, favored mTOR inactivation during lysosomal damage vs. the stress granule formation. Thus, cells utilize Atg8ylation as a response to membrane stress for specific outcomes beyond the process of autophagy, which include the coordinated stress granule formation and mTOR inactivation during lysosomal damage
HostingRepositoryMassIVE
AnnounceDate2022-09-27
AnnouncementXMLSubmission_2022-09-27_08:29:06.975.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBrett Phinney
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListOxidation; Carbamidomethyl
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-24 12:20:58ID requested
12022-09-27 08:29:07announced
Publication List
no publication
Keyword List
submitter keyword: Atg8ylation , mTOR, lysosomal damage
Contact List
Vojo Deretic
contact affiliationUniversity of New Mexico Health Sciences
contact emailvderetic@salud.unm.edu
lab head
Brett Phinney
contact affiliationUC Davis
contact emailbrettsp@ucdavis.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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