scholarly journals Iron homeostasis and plant immune responses: Recent insights and translational implications

2020 ◽  
Vol 295 (39) ◽  
pp. 13444-13457 ◽  
Author(s):  
John H. Herlihy ◽  
Terri A. Long ◽  
John M. McDowell
Keyword(s):  
Iron Deficiency ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Iron Acquisition ◽  
Plant Immunity ◽  
Critical Role ◽  
Critical Factor ◽  
Hormone Signaling ◽  
Natural Ecosystems ◽  
Oxygen Intermediates

Iron metabolism and the plant immune system are both critical for plant vigor in natural ecosystems and for reliable agricultural productivity. Mechanistic studies of plant iron home-ostasis and plant immunity have traditionally been carried out in isolation from each other; however, our growing understanding of both processes has uncovered significant connections. For example, iron plays a critical role in the generation of reactive oxygen intermediates during immunity and has been recently implicated as a critical factor for immune-initiated cell death via ferroptosis. Moreover, plant iron stress triggers immune activation, suggesting that sensing of iron depletion is a mechanism by which plants recognize a pathogen threat. The iron deficiency response engages hormone signaling sectors that are also utilized for plant immune signaling, providing a probable explanation for iron-immunity cross-talk. Finally, interference with iron acquisition by pathogens might be a critical component of the immune response. Efforts to address the global burden of iron deficiency–related anemia have focused on classical breeding and transgenic approaches to develop crops biofortified for iron content. However, our improved mechanistic understanding of plant iron metabolism suggests that such alterations could promote or impede plant immunity, depending on the nature of the alteration and the virulence strategy of the pathogen. Effects of iron biofortification on disease resistance should be evaluated while developing plants for iron biofortification.

scholarly journals Hepcidin: A Critical Regulator of Iron Metabolism during Hypoxia

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Korry J. Hintze ◽  
James P. McClung
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Absorption ◽  
Iron Acquisition ◽  
Iron Status ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Response Element ◽  
Hypoxia Response ◽  
Hepcidin Expression

Iron status affects cognitive and physical performance in humans. Recent evidence indicates that iron balance is a tightly regulated process affected by a series of factors other than diet, to include hypoxia. Hypoxia has profound effects on iron absorption and results in increased iron acquisition and erythropoiesis when humans move from sea level to altitude. The effects of hypoxia on iron balance have been attributed to hepcidin, a central regulator of iron homeostasis. This paper will focus on the molecular mechanisms by which hypoxia affects hepcidin expression, to include a review of the hypoxia inducible factor (HIF)/hypoxia response element (HRE) system, as well as recent evidence indicating that localized adipose hypoxia due to obesity may affect hepcidin signaling and organismal iron metabolism.

Revisiting Iron Metabolism, Iron Homeostasis and Iron Deficiency Anemia

2021 ◽  
Vol 67 (03/2021) ◽  
Author(s):  
Muhammad Saboor ◽  
Amtuz Zehra ◽  
Hassan Hamali ◽  
Abdullah Mobarki
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Deficiency Anemia

scholarly journals Nitric oxide and oxidative stress (H2O2) control mammalian iron metabolism by different pathways.

1996 ◽  
Vol 16 (7) ◽  
pp. 3781-3788 ◽  
Author(s):  
K Pantopoulos ◽  
G Weiss ◽  
M W Hentze
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
De Novo ◽  
Reactive Oxygen ◽  
Target Cells ◽  
Induction Phase ◽  
Reactive Oxygen Intermediate ◽  
Oxygen Intermediates

Several cellular mRNAs are regulated posttranscriptionally by iron-responsive elements (IREs) and the cytosolic IRE-binding proteins IRP-1 and IRP-2. Three different signals are known to elicit IRP-1 activity and thus regulate IRE-containing mRNAs: iron deficiency, nitric oxide (NO), and the reactive oxygen intermediate hydrogen peroxide (H2O2). In this report, we characterize the pathways for IRP-1 regulation by NO and H2O2 and examine their effects on IRP-2. We show that the responses of IRP-1 and IRP-2 to NO remarkably resemble those elicited by iron deficiency: IRP-1 induction by NO and by iron deficiency is slow and posttranslational, while IRP-2 induction by these inductive signals is slow and requires de novo protein synthesis. In contrast, H2O2 induces a rapid posttranslational activation which is limited to IRP-1. Removal of the inductive signal H2O2 after < or = 15 min of treatment (induction phase) permits a complete IRP-1 activation within 60 min (execution phase) which is sustained for several hours. This contrasts with the IRP-1 activation pathway by NO and iron depletion, in which NO-releasing drugs or iron chelators need to be present during the entire activation phase. Finally, we demonstrate that biologically synthesized NO regulates the expression of IRE-containing mRNAs in target cells by passive diffusion and that oxidative stress endogenously generated by pharmacological modulation of the mitochondrial respiratory chain activates IRP-1, underscoring the physiological significance of NO and reactive oxygen intermediates as regulators of cellular iron metabolism. We discuss models to explain the activation pathways of IRP-1 and IRP-2. In particular, we suggest the possibility that NO affects iron availability rather than the iron-sulfur cluster of IRP-1.

The Molecular Signature of Iron Metabolism in Polycythaemia Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3579-3579
Author(s):  
Armin Schumacher ◽  
Henry Mok ◽  
Agnieszka E. Mlodnicka ◽  
Matthias W. Hentze ◽  
Martina Muckenthaler
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Metabolism ◽  
Transcription Initiation ◽  
Positional Cloning ◽  
Iron Homeostasis ◽  
Iron Bioavailability ◽  
Molecular Signature ◽  
Dynamic Changes ◽  
Anemia Of Chronic Disease

Abstract Recent positional cloning of the radiation-induced polycythaemia (Pcm) mutation revealed a 58-bp microdeletion in the promoter region of ferroportin 1 (Fpn1), the sole cellular iron exporter identified to date. The microdeletion causes aberrant transcription initiation and results in the absence of the iron-responsive element in the 5′ untranslated region of the vast majority of Fpn1 transcripts, thereby disrupting translational regulation of Fpn1 expression. Pcm mutant mice exhibit the gamut of iron balance disorders, ranging from iron deficiency at birth to tissue iron overload by young adulthood. Consistent with the perinatal iron deficiency, Pcm pups display a microcytic, hypochromic anemia. Strikingly, the majority of young adult Pcm heterozygous animals display a transient erythropoietin (Epo)-dependent polycythemia with peak hematocrits of up to 80%, eponymous of the mutant strain. Here we report a molecular definition of the regulatory mechanisms governing the dynamic changes in iron balance in Pcm heterozygous mice between 3 and 12 weeks of age. Therein, hepatic and/or duodenal response patterns of iron transporters, such as Trfr, cybrd1 and Slc11a2, defined the transition from early postnatal iron deficiency to iron overload by 12 weeks of age. A significant delay in developmental upregulation of hepcidin (Hamp), the pivotal hormonal regulator of iron homeostasis, correlated with high levels of Fpn1 expression in hepatic Kupffer cells during postnatal development. Conversely, upon upregulation of Hamp expression at 12 weeks of age, Fpn1 expression decreased, indicative of a Hamp-mediated homeostatic loop. Aged cohorts of Pcm mice exhibited low levels of Fpn1 expression in the context of an iron-deficiency erythropoiesis and profound iron sequestration in reticuloendothelial macrophages, duodenum and other tissues. Similar to the anemia of chronic disease, these findings are consistent with decreased iron bioavailability due to sustained downregulation of Fpn1 levels by Hamp. Therefore, iron-deficiency erythropoiesis marks both the beginning and the endpoint of the hematopoietic defects in Pcm mice. However, whereas the embryonic/perinatal anemia results from primary organismal iron deficiency, adult Pcm mice develop anemia due to decreased iron bioavailability despite organismal iron overload. The polycythemia develops at the transition phase between the two disease states, governed by unimpeded Epo signaling. We conclude that regulatory alleles, such as Pcm, with highly dynamic changes in iron balance are ideally suited to interrogate the genetic circuitry regulating iron metabolism.

scholarly journals Role of Fermented Goat Milk on Liver Gene and Protein Profiles Related to Iron Metabolism during Anemia Recovery

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1336
Author(s):  
Jorge Moreno-Fernandez ◽  
María J. M. Alférez ◽  
Inmaculada López-Aliaga ◽  
Javier Díaz-Castro
Keyword(s):  
Iron Deficiency ◽  
Protein Expression ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Goat Milk ◽  
Milk Consumption ◽  
Gene And Protein Expression ◽  
Key Genes ◽  
Liver Gene

Despite the crucial role of the liver as the central regulator of iron homeostasis, no studies have directly tested the modulation of liver gene and protein expression patterns during iron deficiency instauration and recovery with fermented milks. Fermented goat milk consumption improves the key proteins of intestinal iron metabolism during iron deficiency recovery, enhancing the digestive and metabolic utilization of iron. The aim of this study was to assess the influence of fermented goat or cow milk consumption on liver iron homeostasis during iron-deficiency anemia recovery with normal or iron-overload diets. Analysis included iron status biomarkers, gene and protein expression in hepatocytes. In general, fermented goat milk consumption either with normal or high iron content up-regulated liver DMT1, FPN1 and FTL1 gene expression and DMT1 and FPN1 protein expression. However, HAMP mRNA expression was lower in all groups of animals fed fermented goat milk. Additionally, hepcidin protein expression decreased in control and anemic animals fed fermented goat milk with normal iron content. In conclusion, fermented goat milk potentiates the up-regulation of key genes coding for proteins involved in iron metabolism, such as DMT1, and FPN1, FTL1 and down-regulation of HAMP, playing a key role in enhanced iron repletion during anemia recovery, inducing a physiological adaptation of the liver key genes and proteins coordinated with the fluctuation of the cellular iron levels, favoring whole-body iron homeostasis.

scholarly journals Ferroportin 3 is a dual-targeted mitochondrial/chloroplast iron exporter necessary for iron homeostasis in Arabidopsis

2020 ◽  
Author(s):  
Leah J. Kim ◽  
Kaitlyn M. Tsuyuki ◽  
Fengling Hu ◽  
Emily Y. Park ◽  
Jingwen Zhang ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Physiological Role ◽  
Chloroplast Ultrastructure ◽  
Iron Regulation ◽  
Wild Type ◽  
Mitochondrial Ultrastructure ◽  
Iron Deficient

ABSTRACTMitochondria and chloroplasts are organelles with high iron demand that are particularly susceptible to iron-induced oxidative stress. Despite the necessity of strict iron regulation in these organelles, much remains unknown about mitochondrial and chloroplast iron transport in plants. Here, we propose that Arabidopsis Ferroportin 3 (FPN3) is an iron exporter dual-targeted to mitochondria and chloroplasts. FPN3 is expressed in shoots regardless of iron conditions, but its transcripts accumulate under iron deficiency in roots. fpn3 mutants cannot grow as well as wild type under iron-deficient conditions and shoot iron levels are reduced in fpn3 mutants compared to wild type. ICP-MS measurements show that iron levels in the mitochondria and chloroplasts are increased relative to wild type, consistent with the proposed role of FPN3 as a mitochondrial/plastid iron exporter. In iron deficient fpn3 mutants, abnormal mitochondrial ultrastructure was observed, whereas chloroplast ultrastructure was not affected, implying that FPN3 plays a critical role in the mitochondria. Overall, our study suggests that FPN3 is essential for optimal iron homeostasis.Significance statementIron homeostasis must be tightly controlled in the mitochondria and chloroplasts, but iron trafficking in these organelles is not fully understood. Our work suggests that FPN3 is an iron exporter required for maintaining proper iron levels in mitochondria and chloroplasts. Furthermore, FPN3 is necessary for the optimal growth and normal mitochondrial ultrastructure under iron deficiency. This study reveals the physiological role of FPN3 and advances our understanding of iron regulation in mitochondria and chloroplasts.

scholarly journals The Adaptive Mechanism of Plants to Iron Deficiency via Iron Uptake, Transport, and Homeostasis

2019 ◽  
Vol 20 (10) ◽  
pp. 2424 ◽  
Author(s):  
Xinxin Zhang ◽  
Di Zhang ◽  
Wei Sun ◽  
Tianzuo Wang
Keyword(s):  
Iron Deficiency ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Iron Acquisition ◽  
Essential Element ◽  
Transport Mechanisms ◽  
Iron Storage ◽  
Iron Deficient ◽  
Dicotyledonous Plants ◽  
Shed Light

Iron is an essential element for plant growth and development. While abundant in soil, the available Fe in soil is limited. In this regard, plants have evolved a series of mechanisms for efficient iron uptake, allowing plants to better adapt to iron deficient conditions. These mechanisms include iron acquisition from soil, iron transport from roots to shoots, and iron storage in cells. The mobilization of Fe in plants often occurs via chelating with phytosiderophores, citrate, nicotianamine, mugineic acid, or in the form of free iron ions. Recent work further elucidates that these genes’ response to iron deficiency are tightly controlled at transcriptional and posttranscriptional levels to maintain iron homeostasis. Moreover, increasing evidences shed light on certain factors that are identified to be interconnected and integrated to adjust iron deficiency. In this review, we highlight the molecular and physiological bases of iron acquisition from soil to plants and transport mechanisms for tolerating iron deficiency in dicotyledonous plants and rice.

scholarly journals The mitochondrial ABC transporter Atm1 plays a role in iron metabolism and virulence in the human fungal pathogen Cryptococcus neoformans

2017 ◽  
Vol 56 (4) ◽  
pp. 458-468 ◽  
Author(s):  
Eunsoo Do ◽  
Seho Park ◽  
Ming-Hui Li ◽  
Jia-Mei Wang ◽  
Chen Ding ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Abc Transporter ◽  
Iron Metabolism ◽  
Fungal Pathogen ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Processes ◽  
Human Fungal Pathogen ◽  
Mitochondrial Functions

Abstract Iron–sulfur clusters (ISC) are indispensable cofactors for essential enzymes in various cellular processes. In the model yeast Saccharomyces cerevisiae, the precursor of ISCs is exported from mitochondria via a mitochondrial ABC transporter Atm1 and used for cytosolic and nuclear ISC protein assembly. Although iron homeostasis has been implicated in the virulence of the human fungal pathogen Cryptococcus neoformans, the key components of the ISC biosynthesis pathway need to be fully elucidated. In the current study, a homolog of S. cerevisiae Atm1 was identified in C. neoformans, and its function was characterized. We constructed C. neoformans mutants lacking ATM1 and found that deletion of ATM1 affected mitochondrial functions. Furthermore, we observed diminished activity of the cytosolic ISC-containing protein Leu1 and the heme-containing protein catalase in the atm1 mutant. These results suggested that Atm1 is required for the biosynthesis of ISCs in the cytoplasm as well as heme metabolism in C. neoformans. In addition, the atm1 mutants were avirulent in a murine model of cryptococcosis. Overall, our results demonstrated that Atm1 plays a critical role in iron metabolism and virulence for C. neoformans.

scholarly journals ГЕПСИДИН, ТРАНСФЕРИН, ФЕРИТИН: ФІЗІОЛОГІЧНА РОЛЬ ЯК ЦЕНТРАЛЬНИХ РЕГУЛЯТОРІВ ОБМІНУ ЗАЛІЗА В ОРГАНІЗМІ

2019 ◽  
pp. 8-16
Author(s):  
Станіслав Видиборець ◽  
Дмитро Борисенко
Keyword(s):  
Iron Deficiency ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Physiological Role ◽  
Clinical Importance ◽  
Dynamic Parameter ◽  
The Body ◽  
Deficiency Anemia ◽  
Laboratory Diagnostics ◽  
The Given

The knowledge about mammalian iron metabolism has advanced dramatically over the past decades. Studies of genetics, biochemistry and molecular biology allowed us the identification and characterization of many of the molecules involved in regulation of iron homeostasis. Important progresses were made after the discovery in 2000 of a small peptide – hepsidin – that has been proved to play a central role in orchestration on iron metabolism also providing a link between iron metabolism and inflammation and innate immunity. Hepsidin directly interacts with ferroportin, the only known mammalian iron exporter, which is expressed by enterocytes, macrophages and hepatocytes. The direct hepsidin- ferroportin interaction allows an adaptative response from the body in situations that alter normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and inflammation). In clause the items of information on transport protein of iron - transferrin are stated. Its physiological role and clinical importance is shown. Dynamics of the contents of the hepsidin, transferrin, ferritin in persons with latent deficiency of iron. The conclusion about importance of the given parameter for laboratory diagnostics of iron deficiency condition is made. In the article the items of information about the ferritin - protein - depot of iron in body are given. Its physiological role and clinical importance is displayed. Dynamics of changes of the contents ferritin during treatment of the patients with iron deficiency anemia and persons with latent deficiency of iron is shown. The conclusion about the level of the ferritin in serum of blood is the important dynamic parameter for laboratory diagnostics iron deficiency of condition is made.

Iron metabolism and its disorders

2020 ◽  
pp. 5371-5402
Author(s):  
Timothy M. Cox ◽  
John B. Porter
Keyword(s):  
Public Health ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Screening Methods ◽  
Iron Storage ◽  
Poor Countries ◽  
Resource Poor ◽  
Public Health Challenge ◽  
Molecular Pathophysiology

Iron deficiency and iron storage disease—the latter principally due to inherited and acquired anaemias such as thalassemia—are disorders of massive clinical significance across the globe. Iron deficiency is the commonest cause of anaemia, affecting about 1 billion people, and about 0.75 million people have thalassaemia. Largely neglected by health services in rich and resource-poor countries alike, disorders of iron metabolism, whether inherited, nutritional, or otherwise, represent a long-standing public health challenge. Improved screening methods for detection, diagnosis, and appropriate supplementation—as well as genetic counselling—can offer a great deal to relieve the burden in stricken communities. Advances in chelation therapy have improved the survival of patients with iron-loading anaemias and transfusion-related haemochromatosis, and better understanding of the molecular pathophysiology of iron homeostasis now offers the prospect of definitive therapies to control pathological erythropoiesis and the inappropriate drive to acquire lethal quantities of toxic iron.

Sign in / Sign up

Export Citation Format

Share Document