PXD016675

PXD016675 is an original dataset announced via ProteomeXchange.

Title	Cathepsin L is required for autolysosomal clearance in Drosophila
Description	Autophagy is a highly conserved lysosomal degrative pathway important for maintaining cellular homeostasis. Much of our current knowledge of autophagy is focused on the initiation steps with the later steps, particularly lysosomal fusion leading to autolysosome formation and the subsequent role of lysosomal enzymes in degradation and recycling become evident. Autophagy can function in both cell survival and cell death, however the mechanisms that distinguish adaptive/survival autophagy from autophagy-dependent cell death remains to be established. Here we use a proteomic analysis of larval midguts during degradation identifying a group of proteins with peptidase activity, suggesting a role in autophagy-dependent cell death. We show that Cathepsin L deficient Drosophila larval midgut cells, accumulate autophagic vesicles due to a block in autophagic flux, yet midgut degradation in not compromised. The accumulation of large aberrant autolysosomes in the absence of Cathepsin function appears to be the consequence of decreased degradative capacity as they contain undigested cytoplasmic material rather and not due to a defect in autophagosome-lysosome fusion. Finally, we find that other Cathepsins are also required for proper autolysosomal degradation in Drosophila larval midgut cells and that this is conserved in mammalian cells. Our findings suggest that Cathepsins play an important degrative role in the autolysosome to maintain autophagy flux, by balancing autophagosome production and turnover (to prevent autophagic stress).
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_09:56:09.461.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrod Sandow
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	No PTMs are included in the dataset
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-10 02:54:21	ID requested
⏵ 1	2022-02-15 09:56:10	announced

Xu T, Nicolson S, Sandow JJ, Dayan S, Jiang X, Manning JA, Webb AI, Kumar S, Denton D, . Autophagy, 17(10):2734-2749(2021) [pubmed]

submitter keyword: Cathepsin, proteomics, Drosophila

Sharad Kumar
contact affiliation	Co-Director of Institute
contact email	sharad.kumar@unisa.edu.au
lab head
Jarrod Sandow
contact affiliation	WEHI
contact email	sandow@wehi.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD016675

PRIDE project URI

• PRIDE
  1. PXD016675
     1. Label: PRIDE project
     2. Name: Cathepsin L is required for autolysosomal clearance in Drosophila