PXD069825-1

PXD069825 is an original dataset announced via ProteomeXchange.

Title	VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair
Description	Perturbations in lysosome integrity are frequently linked to neurological disorders and ageing, but the underlying pathogenic mechanisms are incompletely understood. Using an unbiased proteomic approach, we here identified the bridge-like lipid transport protein VPS13C/PARK23 as a key component of a global early response pathway to lysosome damage. VPS13C readily binds lysosomes under mechanical or osmotic tension in anticipation of membrane lesions. The latter trigger a conformational change in the protein’s C-terminus, involving its ATG2C domain acting as sensor of damage-induced lipid packing defects. We show that ER-lysosome contacts formed by VPS13C provide critical binding platforms for OSBP/ORPs to enable efficient ER wrapping of damaged lysosomes. A chemical approach to assess directional ER-to-lysosome lipid transport revealed that VPS13C is essential for large-scale lipid delivery to acutely damaged lysosomes to facilitate their repair. Our findings offer new mechanistic insights into how loss-of-function mutations in VPS13C may enhance the risk of Parkinson’s disease.
HostingRepository	PRIDE
AnnounceDate	2026-07-13
AnnouncementXML	Submission_2026-07-13_02:55:56.083.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bianca Esch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-23 06:18:20	ID requested
⏵ 1	2026-07-13 02:55:56	announced

10.1038/S41467-026-75145-Y;

submitter keyword: Human, lysosomal repair, VPS13C, lysosome purification

Florian Fröhlich
contact affiliation	Division of Bioanalytical Chemistry, Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany
contact email	florian.froehlich@uni-osnabrueck.de
lab head
Bianca Esch
contact affiliation	Osnabrück University
contact email	bianca.esch@uos.de
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/2026/07/PXD069825

PRIDE project URI

• PRIDE
  1. PXD069825
     1. Label: PRIDE project
     2. Name: VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair