PXD055240-1

PXD055240 is an original dataset announced via ProteomeXchange.

Title	Label-free LC-MSMS proteomics for P30 Acox1 WT vs KO
Description	Background: Dyslipidemia is a significant contributor to many eye diseases and the lipid processing pathways are not well understood. Peroxisomes oxidize very long-chain, monocarboxylic and dicarboxylic fatty acids. Genetic mutations in peroxisomal proteins may lead to severe neural retinal degeneration. However, there are limited approaches available for peroxisomal disease treatment. Method: In mice with genetic deficiency of ACOX1 (acyl-coenzyme A oxidase 1, the first and key metabolic enzyme in peroxisomal fatty acid oxidation), we characterized the retinal phenotype during development. Retinal function, thickness and photoreceptor structure were examined. Proteomics was utilized for molecular mechanistic investigation. Metabolomics and fatty acid profiling and were conducted to study the metabolic alterations in the retinas. Nutrient intervention was also applied to test if supplementation of lacking nutrients attenuated retinal dysfunction. Results: In one-month-old mice with ACOX1 deficiency, we found reduced neural retinal signaling, accompanied with decrease expression of genes involved in phototransduction. Proteomics identified decreased glucose and mitochondrial metabolism, supported by decreased mitochondrial DNA copy number. Metabolomics showed decreased retinal pyruvate and pyruvate supplementation from one-month old attenuated neural retinal dysfunction in ACOX1-deficient mice at 2 months. Furthermore, there was also a significant decrease in omega-3 fatty acids and a compensatory increase in omega-6 fatty acids. Dietary supplementation of docosahexaenoic acid (omega-3) or docosahexaenoic acid plus arachidonic acid (omega-6) improved neural retinal function in ACOX1-deficient mice. Conclusion: Retinal metabolic imbalance was observed in mice with peroxisomal fatty acid dysfunction. Nutrient intervention is an effective approach to attenuate the disease progression.
HostingRepository	PRIDE
AnnounceDate	2025-12-15
AnnouncementXML	Submission_2025-12-14_17:12:14.327.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD055240
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Zhongjie Fu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-27 05:55:48	ID requested
⏵ 1	2025-12-14 17:12:15	announced

Boeck M, Yagi H, Chen CT, Zeng Y, Lee D, Nian S, Kasai T, Lee J, Hirst V, Wang C, Neilsen K, Rodrick TC, McCutcheon A, Yu M, Lodhi IJ, Singh SA, Aikawa M, Bazinet RP, Fu Z, Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation. J Adv Res, 78():667-680(2025) [pubmed]

10.1016/j.jare.2025.03.004;

10.6019/PXD055240;

submitter keyword: LC-MSMS, retinas,Peroxisome, Acox1

Zhongjie Fu
contact affiliation	Boston Children's Hospital
contact email	Zhongjie.fu@childrens.harvard.edu
lab head
Zhongjie Fu
contact affiliation	Boston Children's Hospital
contact email	zhongjie.fu@childrens.harvard.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/2025/12/PXD055240

PRIDE project URI

• PRIDE
  1. PXD055240
     1. Label: PRIDE project
     2. Name: Label-free LC-MSMS proteomics for P30 Acox1 WT vs KO