PXD082136-1

PXD082136 is an original dataset announced via ProteomeXchange.

Title	Super-resolution imaging reveals an ER-resident VHL–DEGS1 axis controlling ER-phagy and renal carcinoma growth
Description	The von Hippel–Lindau tumor suppressor pVHL is best known as an E3 ligase substrate-recognition component that controls hypoxia-inducible factor stability, but how VHL mutations perturb organelle homeostasis in renal carcinoma remains unclear. Here, using live-cell super-resolution microscopy and CRISPR–Cas9 endogenous tagging, we found that endogenous pVHL is enriched in compact ER nest-like domains associated with lipid droplet formation and peroxisome dynamics. Pathogenic VHL mutations preserved ER-domain localization but induced ER remodeling, lysosome-associated ER vesicles and enhanced ER-phagy. Proteomic analysis of VHL-mutant renal carcinoma models and patient specimens identified the ER-resident sphingolipid desaturase DEGS1 as a mutation-associated effector. DEGS1 upregulation increased the ceramide/dihydroceramide ratio, enhanced ER–mitochondria coupling and promoted mitochondrial fission, whereas DEGS1 depletion reversed these phenotypes and suppressed tumor growth. These effects were not rescued by HIF2α depletion, and pharmacological DEGS1 inhibition enhanced HIF2α blockade. Together, our findings reveal an endogenous VHL-associated ER microdomain and identify a DEGS1-dependent lipid-organelle remodeling program that promotes VHL-mutant renal carcinoma adaptation.
HostingRepository	iProX
AnnounceDate	2026-08-04
AnnouncementXML	Submission_2026-08-04_00:45:22.356.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenmin Tian
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-04 00:44:52	ID requested
⏵ 1	2026-08-04 00:45:22	announced

Dataset with its publication pending

submitter keyword: VHL, DEGS1,mitochondrial dynamics,renal cell carcinoma,organelle homeostasis

Yang Chen
contact affiliation	The Center for Precision Medicine Multi-omics Research (CPMMR)
contact email	chenyang1816185048@bjmu.edu.cn
lab head
Wenmin Tian
contact affiliation	The Center for Precision Medicine Multi-omics Research (CPMMR)
contact email	tianwenmin2019@126.com
dataset submitter

iProX dataset URI