PXD052634

PXD052634 is an original dataset announced via ProteomeXchange.

Title	The landscape of renal protein cysteine acylation in mice with kidney injury induced by a high fat diet
Description	Background. Dyslipidemia is associated with chronic kidney disease (CKD). It has been shown that inhibition of β-oxidation and lipid accumulation are common threats in the onset of kidney injury and conducive to fibrosis. We characterized the S-acylated proteome of kidneys from mice with diet-induced nephropathy, to uncover novel lipid-related biochemical changes that might contribute to the lipid-induced kidney dysfunction. Methods. We conducted total and S-acylated proteomics, and lipidomics of the renal crude membrane fractions of mice fed a high-fat diet (HFD). Then, we investigated in vitro the effect of S-acylation inhibition on megalin expression and ligand binding. Results. HFD caused albuminuria with unchanged kidney function. The dietary intervention induced a large-scale repression of protein S-acylation as well as of the most abundant ceramides and sphingomyelin species, which are highly suggestive of an overall reduction in acyl-CoA availability. S-acylation repression mostly affected proteins involved in endocytosis and intracellular transport. In particular, the kidney of the mice fed a HFD, which are characterized by albuminuria, displayed a marked decrease in the total amount and in the S-acylated form of megalin, the main tubular protein retrieval system. Further in vitro experiments indicated that S-acylation is important for total expression of megalin. Conclusions. The diet-induced derangement of fatty acids metabolism modifies the renal landscape of the S-acylated proteome during early stage of the kidney injury, which might reduce the maximal capacity of protein reabsorption by the proximal tubule.
HostingRepository	PRIDE
AnnounceDate	2025-03-21
AnnouncementXML	Submission_2025-03-21_11:42:20.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Witold Wolski
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-28 07:33:58	ID requested
⏵ 1	2025-03-21 11:42:21	announced

10.1038/s41598-025-92530-7;

Xiu F, Gai Z, Gehrig P, Wolski WE, Lone MA, Visentin M, The landscape of renal protein S-acylation in mice with lipid-induced nephrotoxicity. Sci Rep, 15(1):7689(2025) [pubmed]

submitter keyword: HF-diet, DIA, Whole Proteome, PALMITOYLATED,Mus Musculus, Chow-diet, Proteomics

Dr. Michele Visentin
contact affiliation	University Hospital of Zurich (USZ)
contact email	michele.visentin@usz.ch
lab head
Witold Wolski
contact affiliation	Functional Genomics Center Zurch
contact email	wew@fgcz.ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052634
     1. Label: PRIDE project
     2. Name: The landscape of renal protein cysteine acylation in mice with kidney injury induced by a high fat diet