PXD031527

PXD031527 is an original dataset announced via ProteomeXchange.

Title	Autophagy cargo receptors are secreted via extracellular vesicles and particles in response to endolysosomal inhibition or impaired autophagosome maturation
Description	The endosome-lysosome (endolysosome) system plays central roles in both autophagic degradation and secretory pathways, including the exocytic release of extracellular vesicles and particles (EVPs). Although previous work has revealed important interconnections between autophagy and EVP-mediated secretion, our molecular understanding of these secretory events during endolysosome inhibition remains incomplete. Here, we delineate a secretory autophagy pathway upregulated in response to endolysosomal inhibition that mediates the EVP-associated extracellular release of autophagic cargo receptors, including p62/SQSTM1. This extracellular secretion is highly regulated and critically dependent on multiple ATGs required for the progressive steps of early autophagosome formation as well as Rab27a-dependent exocytosis. Furthermore, the disruption of autophagosome maturation, either due to genetic inhibition of the autophagosome-to-autolyosome fusion machinery or blockade via the SARS-CoV2 viral protein ORF3a, is sufficient to induce robust EVP-associated secretion of autophagy cargo receptors. Finally, we demonstrate that this ATG-dependent, EVP-mediated secretion pathway buffers against the intracellular accumulation of autophagy cargo receptors when classical autophagic degradation is impaired. Based on these results, we propose that secretory autophagy via EVPs functions as an alternate route to clear sequestered material and maintain proteostasis in response to endolysosomal dysfunction or impaired autophagosome maturation.
HostingRepository	PRIDE
AnnounceDate	2022-03-03
AnnouncementXML	Submission_2022-03-03_10:17:58.680.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yu-Hsiu Lin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-09 05:10:03	ID requested
⏵ 1	2022-03-03 10:17:59	announced

Dataset with its publication pending

submitter keyword: HEK293T, Extracellular Vesicles, TMT, LC-MS/MS

Andrew Leidal
contact affiliation	Department of Pathology, University of California, San Francisco, USA
contact email	andrew.leidal@ucsf.edu
lab head
Yu-Hsiu Lin
contact affiliation	University of California, San Francisco
contact email	lin.yu.hsiu@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031527
     1. Label: PRIDE project
     2. Name: Autophagy cargo receptors are secreted via extracellular vesicles and particles in response to endolysosomal inhibition or impaired autophagosome maturation