New ProteomeXchange dataset PXD051897

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Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD051897

Summary of dataset

Status: new
Identifier: PXD051897
HostingRepository: PRIDE
Species: Mus musculus
Title: IRP1 deficiency triggers metabolic reprograming, increases insulin sensitivity and protects mice against metabolic syndrome pathologies
Submitter: Vincent Richard
LabHead: Christoph H Borchers
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 Ir
p1-/- mice, making them unavailable for gluconeogenesis in the liver. Thus, IRP1 emerges as an important metabolic regulator.

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