PXD074652 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
| 0 | 2026-02-19 15:19:15 | ID requested | |
| ⏵ 1 | 2026-05-02 18:55:46 | announced | |
Publication List
Keyword List
| submitter keyword: Human, Lysosome, LYSET, SILAC, ether-lipid, FAR1 |
Contact List
| 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 | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD074652
- Label: PRIDE project
- Name: Peroxisome-derived ether lipids regulate lysosomal homeostasis through exocytosis control