PXD051897-1

PXD051897 is an original dataset announced via ProteomeXchange.

Title	IRP1 deficiency triggers metabolic reprograming, increases insulin sensitivity and protects mice against metabolic syndrome pathologies
Description	Iron regulatory protein 1 (IRP1) is a post-transcriptional regulator of cellular iron metabolism. Irp1-/- mice are viable but develop polycythemia. We report that these animals also exhibit fasting hypoglycemia and are protected against high fat diet-induced hyperglycemia and liver steatosis. Mechanistically, proteomics analysis revealed mitochondrial dysfunction in Irp1-/-livers. Seahorse assays validated impaired respiratory capacity in primary hepatocytes but also differentiated myotubes from Irp1-/- mice, which caused a switch from oxidative phosphorylation to glycolytic metabolism for energy production. This was accompanied by increased insulin sensitivity and glucose uptake by skeletal muscles. However, under conditions of metabolic stress or iron restriction, IRP1 deficiency prevented appropriate mitochondrial iron supply. Mitochondrial dysfunction and inefficient energy production caused metabolic rewiring and accumulation of metabolites in skeletal muscles of Irp1-/- mice, making them unavailable for gluconeogenesis in the liver. Thus, IRP1 emerges as an important metabolic regulator.
HostingRepository	PRIDE
AnnounceDate	2025-12-17
AnnouncementXML	Submission_2025-12-17_11:53:57.407.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vincent Richard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-30 10:52:18	ID requested
⏵ 1	2025-12-17 11:53:57	announced

Dataset with its publication pending

submitter keyword: proteomics,IRP1, liver, mouse, insulin

Christoph H Borchers
contact affiliation	Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Quebec, H3T 1E2, Canada Gerald Bronfman Department of Oncology, McGill University, Montréal, Quebec H4A 3T2, Canada Department of Pathology, McGill University, Montréal,Quebec H4A 3J1, Canada
contact email	christoph.borchers@mcgill.ca
lab head
Vincent Richard
contact affiliation	Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University
contact email	vincentroyrichard@gmail.com
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/PXD051897

PRIDE project URI

• PRIDE
  1. PXD051897
     1. Label: PRIDE project
     2. Name: IRP1 deficiency triggers metabolic reprograming, increases insulin sensitivity and protects mice against metabolic syndrome pathologies