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PXD022492

PXD022492 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe lysosomal proteome of senescent cells contributes to the senescence-associated secretome
DescriptionSenescent cells accumulate in tissues over time, favoring the onset and progression of multiple age-related diseases. The senescence-associated secretory phenotype (SASP) is considered the main pathological feature of senescent cells, however, little is known about the mechanism of secretion of SASP factors. Here, we report that human senescent cells present higher levels of the two main types of authophagy, namely macroautophagy (MA) and chaperone-mediated autophagy (CMA), together with an increase in the transcription factor TFEB and in lysosomal mass. Proteomic analyses showed profound and widespread changes in the composition of lysosomal substrates in both CMA- and MA-derived lysosomes. Notably, some proteins previously identified as plasma biomarkers of aging in humans are highly enriched in the lysosomes of senescent cells, as it is the case of cathepsin D (CTSD). Moreover, we found that senescent cells have the ability to perform lysosomal exocytosis in a RAB27A-dependent manner and this is the main route for the secretion of multiple cytokines (such as CCL2, CCL3, CXCL12), the protease inhibitor SERPINE1 and protease CTSD. We conclude that lysosomes are hyperactive in senescent cells, display an altered pattern of constitutive proteins and lysosomal substrates, and undergo exocytosis contributing to the SAS
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:51:49.651.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFernando Garcia
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-11-12 06:33:58ID requested
12022-08-29 01:39:38announced
22023-11-14 08:51:50announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Lysosomes, Senescence, Macroautophagy, Protein Degradation., Chaperone-mediated autophagy
Contact List
Javier Muñoz Peralta
contact affiliationJavier Muñoz, PhD - Head of Proteomics Unit Spanish National Cancer Research Centre (CNIO) Address: Melchor Fernández Almagro, 3. 28029 Madrid. SPAIN Phone: +34 917 328 000 Ext. 3110
contact emailjmunozpe@cnio.es
lab head
Fernando Garcia
contact affiliationFernando García Martínez, Ph.D. Proteomics Unit, Spanish National cancer Research Center, CNIO, MADRID, SPAIN
contact emailfgarcia@cnio.es
dataset submitter
Full Dataset Link List
Dataset FTP location
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