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PXD048258-1

PXD048258 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA mechanism that transduces lysosomal damage signals to stress granule formation for cell survival
DescriptionLysosomal damage is a major threat to cell survival. Our previous work has reported that lysosomal damage induces stress granule (SG) formation. However, the significance of SG formation on cell fate and the precise mechanisms by which lysosomal damage triggers SG formation remains unclear. Here, we show that SG formation is initiated through a novel calcium-dependent pathway and plays a significant role in promoting cell survival in response to lysosomal damage. Mechanistically, we demonstrate that during lysosomal damage, ALIX (ALG2-interacting protein X) together with its partner, the calcium-binding protein ALG2, transduces lysosomal damage signals by detecting calcium leakage to induce SG formation by controlling the phosphorylation of eIF2alpah. ALIX facilities SG formation by coordinating the upstream regulation of eIF2alpha phosphorylation via PKR and PACT. We also found this regulatory event of SG formation occur on damaged lysosomes. Collectively, these investigations reveal novel insight into the precise regulation of SG formation, and the interaction between damaged lysosomes and stress granules. Importantly, SG formation is significant for promoting cell survival in the physiological context of lysosomal damage inflicted by SARS-CoV-2 ORF3a, adenovirus infection, Malaria hemozoin, proteopathic tau as well as environmental hazard silica.
HostingRepositoryMassIVE
AnnounceDate2024-07-16
AnnouncementXMLSubmission_2024-07-16_15:31:56.078.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 Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-04 13:41:03ID requested
12024-07-16 15:31:56announced
Publication List
no publication
Keyword List
submitter keyword: lysosomal damage
Contact List
Jingyue Jia
contact affiliationCenter for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center
contact emailJJia@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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