PXD074652

PXD074652 is an original dataset announced via ProteomeXchange.

Title	Peroxisome-derived ether lipids regulate lysosomal homeostasis through exocytosis control
Description	Lysosomes and peroxisomes are essential for cellular homeostasis, yet how their activities are coordinated remains poorly understood. Here, we identify peroxisome-derived ether lipids as key regulators of lysosomal function. A genome-wide CRISPR/Cas9 screen in Mucolipidosis V (LYSET-deficient) cells revealed that disruption of ether lipid synthesis genes or peroxins markedly reduces lysosome accumulation and restores degradative capacity. Genetic or pharmacological inhibition of ether lipid synthesis enhanced lysosomal exocytosis through TRPML1- and SNARE-dependent pathways, promoting clearance of undigested material independently of mannose-6-phosphate trafficking. Conversely, supplementation with the ether lipid precursor hexadecylglycerol increased lysosome abundance and impaired digestion. These findings uncover a peroxisome–lysosome metabolic axis in which ether lipids act as bidirectional regulators of lysosomal number and function independent of the lysosomal master regulator TFEB. This mechanism reveals how lipid metabolism modulates lysosomal homeostasis and provides insights into potential new strategies to combat lysosomal and peroxisomal disorders.
HostingRepository	PRIDE
AnnounceDate	2026-05-03
AnnouncementXML	Submission_2026-05-02_18:55:45.792.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD074652
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Liang Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-19 15:19:15	ID requested
⏵ 1	2026-05-02 18:55:46	announced

10.1038/S44318-026-00791-3;

10.6019/PXD074652;

submitter keyword: Human, Lysosome, LYSET, SILAC, ether-lipid, FAR1

Ming Li
contact affiliation	Department of Molecular Cellular and Developmental Biology, University of Michigan
contact email	mlium@umich.edu
lab head
Liang Chen
contact affiliation	University of Michigan
contact email	lchenum@umich.edu
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/2026/05/PXD074652

PRIDE project URI

• PRIDE
  1. PXD074652
     1. Label: PRIDE project
     2. Name: Peroxisome-derived ether lipids regulate lysosomal homeostasis through exocytosis control