ArticleThe Journal of biological chemistry2015
Prion protein promotes kidney iron uptake via its ferrireductase activity.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Urine Proteomics as a Source of Biological Information and Outcome Predictor in Living Kidney Transplantation.Molecular & cellular proteomics : MCP · 2026Article
- Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders.Biology · 2025Review
- Single-Cell RNA Sequencing Delineates Renal Anti-Fibrotic Mechanisms Mediated by TRPC6 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Iron metabolism and chronic inflammation in IgA nephropathy.Renal failure · 2023Review
- Review
- Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney.Nature reviews. Nephrology · 2023Review
- Ferroptosis: an important player in the inflammatory response in diabetic nephropathy.Frontiers in immunology · 2023Review
- The (Bio)Chemistry of Non-Transferrin-Bound Iron.Molecules (Basel, Switzerland) · 2022Review
- Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.Molecules (Basel, Switzerland) · 2022Review
- β-Cleavage of the prion protein in the human eye: Implications for the spread of infectious prions and human ocular disorders.Experimental eye research · 2021Article
- Harnessing the Physiological Functions of Cellular Prion Protein in the Kidneys: Applications for Treating Renal Diseases.Biomolecules · 2021Review
- Overdosing on iron: Elevated iron and degenerative brain disorders.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- The cellular prion protein is a stress protein secreted by renal tubular cells and a urinary marker of kidney injury.Cell death & disease · 2020Article
- The multifaceted role of iron in renal health and disease.Nature reviews. Nephrology · 2020Review
- Proximal tubule transferrin uptake is modulated by cellular iron and mediated by apical membrane megalin-cubilin complex and transferrin receptor 1.The Journal of biological chemistry · 2019Article
- Prion protein modulates iron transport in the anterior segment: Implications for ocular iron homeostasis and prion transmission.Experimental eye research · 2018Article
- Prion protein modulates glucose homeostasis by altering intracellular iron.Scientific reports · 2018Article
- New Perspectives on Iron Uptake in Eukaryotes.Frontiers in molecular biosciences · 2018Review
- Orchestrated regulation of iron trafficking proteins in the kidney during iron overload facilitates systemic iron retention.PloS one · 2018Article
- Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner.Frontiers in molecular neuroscience · 2017Article
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9 authors at 2 institutions in 1 country.
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Abstract
Brain iron-dyshomeostasis is an important cause of neurotoxicity in prion disorders, a group of neurodegenerative conditions associated with the conversion of prion protein (PrP(C)) from its normal conformation to an aggregated, PrP-scrapie (PrP(Sc)) isoform. Alteration of iron homeostasis is believed to result from impaired function of PrP(C) in neuronal iron uptake via its ferrireductase activity. However, unequivocal evidence supporting the ferrireductase activity of PrP(C) is lacking. Kidney provides a relevant model for this evaluation because PrP(C) is expressed in the kidney, and ∼370 μg of iron are reabsorbed daily from the glomerular filtrate by kidney proximal tubule cells (PT), requiring ferrireductase activity. Here, we report that PrP(C) promotes the uptake of transferrin (Tf) and non-Tf-bound iron (NTBI) by the kidney in vivo and mainly NTBI by PT cells in vitro. Thus, uptake of (59)Fe administered by gastric gavage, intravenously, or intraperitoneally was significantly lower in PrP-knock-out (PrP(-/-)) mouse kidney relative to PrP(+/+) controls. Selective in vivo radiolabeling of plasma NTBI with (59)Fe revealed similar results. Expression of exogenous PrP(C) in immortalized PT cells showed localization on the plasma membrane and intracellular vesicles and increased transepithelial transport of (59)Fe-NTBI and to a smaller extent (59)Fe-Tf from the apical to the basolateral domain. Notably, the ferrireductase-deficient mutant of PrP (PrP(Δ51-89)) lacked this activity. Furthermore, excess NTBI and hemin caused aggregation of PrP(C) to a detergent-insoluble form, limiting iron uptake. Together, these observations suggest that PrP(C) promotes retrieval of iron from the glomerular filtrate via its ferrireductase activity and modulates kidney iron metabolism.
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