scholarly journals SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron regulatory protein 1

Oncogene ◽  
2014 ◽  
Vol 34 (16) ◽  
pp. 2115-2124 ◽  
Author(s):  
S M Jeong ◽  
J Lee ◽  
L W S Finley ◽  
P J Schmidt ◽  
M D Fleming ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Regulatory Protein ◽  
Cancer Growth ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Iron Regulatory Protein 1

scholarly journals Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nhan Huynh ◽  
Qiuxiang Ou ◽  
Pendleton Cox ◽  
Roland Lill ◽  
Kirst King-Jones
Keyword(s):  
Iron Homeostasis ◽  
Nuclear Translocation ◽  
Regulatory Protein ◽  
Glycogen Metabolism ◽  
Glycogen Storage Disease Type ◽  
Iron Regulatory Protein ◽  
Messenger Rnas ◽  
Branching Enzyme ◽  
Cellular Iron ◽  
Iron Regulatory Protein 1

AbstractIron Regulatory Protein 1 (IRP1) is a bifunctional cytosolic iron sensor. When iron levels are normal, IRP1 harbours an iron-sulphur cluster (holo-IRP1), an enzyme with aconitase activity. When iron levels fall, IRP1 loses the cluster (apo-IRP1) and binds to iron-responsive elements (IREs) in messenger RNAs (mRNAs) encoding proteins involved in cellular iron uptake, distribution, and storage. Here we show that mutations in the Drosophila 1,4-Alpha-Glucan Branching Enzyme (AGBE) gene cause porphyria. AGBE was hitherto only linked to glycogen metabolism and a fatal human disorder known as glycogen storage disease type IV. AGBE binds specifically to holo-IRP1 and to mitoNEET, a protein capable of repairing IRP1 iron-sulphur clusters. This interaction ensures nuclear translocation of holo-IRP1 and downregulation of iron-dependent processes, demonstrating that holo-IRP1 functions not just as an aconitase, but throttles target gene expression in anticipation of declining iron requirements.

HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species

2008 ◽  
Vol 133 (2) ◽  
pp. 167-177 ◽  
Author(s):  
Jin-Mo Gu ◽  
Seung Oe Lim ◽  
Sae Jin Oh ◽  
So-Mi Yoon ◽  
Je Kyung Seong ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Iron Metabolism ◽  
Regulatory Protein ◽  
Reactive Oxygen ◽  
Iron Regulatory Protein ◽  
Oxygen Species ◽  
Iron Regulatory Protein 1

scholarly journals Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma

2021 ◽  
Vol 22 (3) ◽  
Author(s):  
Fengping Yao ◽  
Xiaohong Cui ◽  
Ying Zhang ◽  
Zhuchun Bei ◽  
Hongquan Wang ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Cellular Iron Homeostasis ◽  
Iron Regulatory Protein 1

scholarly journals Regulation of Cellular Iron Metabolism by Erythropoietin: Activation of Iron-Regulatory Protein and Upregulation of Transferrin Receptor Expression in Erythroid Cells

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 680-687 ◽  
Author(s):  
Günter Weiss ◽  
Tracey Houston ◽  
Stefan Kastner ◽  
Karin Jöhrer ◽  
Kurt Grünewald ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Iron Metabolism ◽  
Transferrin Receptor ◽  
Regulatory Protein ◽  
Receptor Expression ◽  
General Mechanism ◽  
Iron Regulatory Protein ◽  
Erythroid Progenitor ◽  
Cellular Iron ◽  
Erythroid Progenitor Cells

Abstract Erythropoietin (Epo) is the central regulator of red blood cell production and acts primarily by inducing proliferation and differentiation of erythroid progenitor cells. Because a sufficient supply of iron is a prerequisite for erythroid proliferation and hemoglobin synthesis, we have investigated whether Epo can regulate cellular iron metabolism. We present here a novel biologic function of Epo, namely as a potential modulator of cellular iron homeostasis. We show that, in human (K562) and murine erythroleukemic cells (MEL), Epo enhances the binding affinity of iron-regulatory protein (IRP)-1, the central regulator of cellular iron metabolism, to specific RNA stem-loop structures, known as iron-responsive elements (IREs). Activation of IRP-1 by Epo is associated with a marked increase in transferrin receptor (trf-rec) mRNA levels in K562 and MEL, enhanced cell surface expression of trf-recs, and increased uptake of iron into cells. These findings are in agreement with the well-established mechanism whereby high-affinity binding of IRPs to IREs stabilizes trf-rec mRNA by protecting it from degradation by a specific RNase. The effects of Epo on IRE-binding of IRPs were not observed in human myelomonocytic cells (THP-1), which indicates that this response to Epo is not a general mechanism observed in all cells but is likely to be erythroid-specific. Our results provide evidence for a direct functional connection between Epo biology and iron metabolism by which Epo increases iron uptake into erythroid progenitor cells via posttranscriptional induction of trf-rec expression. Our data suggest that sequential administration of Epo and iron might improve the response to Epo therapy in some anemias.

Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells

2005 ◽  
Vol 206 (3) ◽  
pp. 275-287 ◽  
Author(s):  
Haobin Chen ◽  
Todd Davidson ◽  
Steven Singleton ◽  
Michael D. Garrick ◽  
Max Costa
Keyword(s):  
Regulatory Protein ◽  
A549 Cells ◽  
Iron Level ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Iron Regulatory Protein 1

scholarly journals Iron Regulatory Protein 1 Outcompetes Iron Regulatory Protein 2 in Regulating Cellular Iron Homeostasis in Response to Nitric Oxide

2011 ◽  
Vol 286 (26) ◽  
pp. 22846-22854 ◽  
Author(s):  
Agnieszka Styś ◽  
Bruno Galy ◽  
Rafal R. Starzyński ◽  
Ewa Smuda ◽  
Jean-Claude Drapier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Cellular Iron ◽  
Cellular Iron Homeostasis ◽  
Iron Regulatory Protein 1

scholarly journals Haem precursor δ-aminolaevulinic acid induces activation of the cytosolic iron regulatory protein 1

1997 ◽  
Vol 328 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Helotonio CARVALHO ◽  
Etelvino José Henriques BECHARA ◽  
Rogério MENEGHINI ◽  
Marilene DEMASI
Keyword(s):  
Methyl Ester ◽  
Regulatory Protein ◽  
Iron Regulatory Protein ◽  
Intracellular Iron ◽  
Aminolaevulinic Acid ◽  
Cellular Iron ◽  
Co Sensor ◽  
Haem Iron ◽  
Fold Activation ◽  
Iron Regulatory Protein 1

Control of cellular iron homoeostasis is performed by iron regulatory protein 1 (IRP1) through post-transcriptional modifications. This protein is sensitive to intracellular iron availability, being activated at low iron levels and inactivated at high iron levels, conditions that signal the increased expression of the transferrin receptor or of ferritin respectively. IRP1 is known to be activated by some oxidants such as H2O2 and NO. Δ-Aminolaevulinic acid (ALA), previously found to produce reactive oxygen species and a carbon-centred radical, to release iron from ferritin, and to increase rat liver and brain non-haem iron and ferritin, was investigated for its effects on IRP1 activity in cultured hamster pulmonary fibroblasts. We have found that 1-2 mM ALA produced a 2-3-fold activation of IRP. On incubation with 1-4 mM succinylacetone methyl ester, a potent ALA dehydratase inhibitor, a 3-4-fold activation of the protein was observed, accompanied by a 40% increase in the intracellular ALA concentration. When cells were incubated in the presence of ALA or succinylacetone methyl ester, N-acetylcysteine inhibited IRP1 activation, suggesting that the observed effect is mediated by an oxidative process. We surmise that ALA-induced IRP1 activation might act as a co-sensor of iron homoeostasis.

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