PXD050916

PXD050916 is an original dataset announced via ProteomeXchange.

Title	Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in Adiponectin receptor 1 (AdipoR1) deficient mice
Description	Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration (AMD). This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 FAs, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α (PPARα) signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium (RPE). Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome (BBS) proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in BBS-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including AMD.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:46:57.382.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fangyuan Gao
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-22 16:14:00	ID requested
1	2024-06-23 01:39:33	announced
⏵ 2	2024-10-22 06:46:59	announced	2024-10-22: Updated project metadata.

Lewandowski D, Gao F, Imanishi S, Tworak A, Bassetto M, Dong Z, Pinto AFM, Tabaka M, Kiser PD, Imanishi Y, Skowronska-Krawczyk D, Palczewski K, Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1-deficient mice. J Biol Chem, 300(5):107291(2024) [pubmed]

10.1016/j.jbc.2024.107291;

submitter keyword: proteomics, lipidomics, retinal pigment epithelium (RPE), retina,Polyunsaturated fatty acids (PUFAs)

Dominik Lewandowski
contact affiliation	Department of Ophthalmology, University of California, Irvine, CA 92697
contact email	lewandod@hs.uci.edu
lab head
Fangyuan Gao
contact affiliation	University of California, Irvine
contact email	fangyuag@hs.uci.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/2024/06/PXD050916

PRIDE project URI

• PRIDE
  1. PXD050916
     1. Label: PRIDE project
     2. Name: Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in Adiponectin receptor 1 (AdipoR1) deficient mice