PXD042079-2

PXD042079 is an original dataset announced via ProteomeXchange.

Title	The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation
Description	Autophagy is a finely orchestrated process required for the lysosomal degradation of cytosolic components. The final degradation step is essential for clearing autophagic cargo and recycling macromolecules. Using a CRISPR/Cas9-based screen, we identify RNAseK, a highly conserved transmembrane protein, as a regulator of autophagosome degradation. Analyses of RNAseK knockout cells reveal that, while autophagosome maturation is intact, cargo degradation is severely disrupted. Importantly, lysosomal protease activity and acidification remain intact in the absence of RNAseK suggesting a specificity to autolysosome degradation. Analyses of lysosome fractions show reduced levels of a subset of hydrolases in the absence of RNAseK. Of these, the knockdown of PLD3 leads to a defect in autophagosome clearance. Furthermore, the lysosomal fraction of RNAseK-depleted cells exhibits an accumulation of the ESCRT-III complex component, VPS4a, which is required for the lysosomal targeting of PLD3. Altogether, here we identify a lysosomal hydrolase delivery pathway required for efficient autolysosome degradation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:52:12.808.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Robert Mosen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-09 00:04:35	ID requested
1	2024-08-02 07:41:15	announced
⏵ 2	2024-10-22 06:52:13	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: DIA-MS,autophagosome degradation, RNAseK,lysosome

Dr Dominic
contact affiliation	Institute for Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn, Germany
contact email	dwin@uni-bonn.de
lab head
Peter Robert Mosen
contact affiliation	Utrecht University Biomolecular Mass Spectrometry and Proteomics Padualaan 8, 3584 CH Utrecht
contact email	p.r.mosen@uu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042079
     1. Label: PRIDE project
     2. Name: The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation