• BACH1
• cardiovascular disease
• stem cell

• Basic-Leucine Zipper Transcription Factors/metabolism
• Basic-Leucine Zipper Transcription Factors/genetics
• Humans
• Animals
• Epithelial-Mesenchymal Transition
• Neoplasms/metabolism
• Neoplasms/genetics

• 92068202 Great Program of National Natural Science Foundation of China
• 82220108020 Great Program of National Natural Science Foundation of China
• 82000293 National Natural Science Foundation of China
• 82370434 National Natural Science Foundation of China
• YESS20210208 Young Elite Scientist Sponsorship Program by CAST
• 22QA1408900 Science and Technology Commission of Shanghai Municipality
• National Natural Science Foundation of China
• Science and Technology Commission of Shanghai Municipality

• Circadian clocks
• IRE
• IRP
• Iron metabolism
• Liver
• Ribosome profiling
• Translation

• Animals
• Iron Regulatory Protein 1/metabolism
• Iron Regulatory Protein 1/genetics
• Iron Regulatory Protein 2/metabolism
• Iron Regulatory Protein 2/genetics
• Circadian Rhythm/genetics
• RNA, Messenger/metabolism
• RNA, Messenger/genetics
• Mice
• Liver/metabolism
• Iron/metabolism
• Gene Expression Regulation
• Response Elements
• Mice, Inbred C57BL
• Male
• Feeding Behavior

• 179190 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• 141735 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• University of Lausanne

• Animals
• Iron/metabolism
• Mice
• Tumor Microenvironment/immunology
• Humans
• Tumor-Associated Macrophages/immunology
• Tumor-Associated Macrophages/metabolism
• CD8-Positive T-Lymphocytes/immunology
• Cell Line, Tumor
• Toll-Like Receptor 2/metabolism
• Toll-Like Receptor 2/immunology
• Mice, Inbred C57BL
• Lipocalin-2/metabolism
• Lipocalin-2/immunology
• Female
• Symbiosis/immunology
• Macrophages/immunology
• Macrophages/metabolism
• Macrophage Activation/immunology
• Mice, Knockout

• ferroportin
• hepcidin
• iron
• miRNA
• suckling

• Rats
• Animals
• Iron/metabolism
• Hepcidins/genetics
• Iron Deficiencies
• Mammals/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• MicroRNAs/genetics
• Cation Transport Proteins

• 32001676 National Natural Science Foundation of China

• BACH1
• Cancer
• Immunity
• Prognostic biomarker
• Targeted therapy

• No. 82173313 National Natural Science Foundation of China
• No. 82273310 National Natural Science Foundation of China
• 2022CFA016 Natural Science Foundation of Hubei Province
• 2023BR038 Basic Research Support Program of Huazhong University of Science and Technology

• Humans
• Hep G2 Cells
• Reactive Oxygen Species/metabolism
• Iron Overload/metabolism
• Iron/metabolism

• Brain
• Iron
• Multivariate analysis
• Rubidium
• Selenium
• Trace elements

• Mice
• Animals
• Trace Elements/analysis
• Selenium
• Magnesium
• Manganese
• Chromium
• Copper
• Cobalt
• Rubidium
• Liver/chemistry
• Brain
• Sodium

• Autophagy
• Cardiomyocytes
• Ferritinophagy
• Inflammaging
• Macrophage
• Proteasome

• Humans
• Iron/metabolism
• Proteolysis
• Anemia/complications
• Inflammation
• Aging/metabolism

• Ferroportin 1 (Fpn1)
• Hepcidin-dependent and -independent pathways
• Iron efflux
• Iron metabolism proteins
• Neurodegenerative disorders

• Animals
• Humans
• Mice
• Rats
• Brain/metabolism
• Iron/metabolism
• Parkinson Disease/metabolism
• Cation Transport Proteins/metabolism

• Bile ducts
• Cell death
• Hepatocytes
• Iron poisoning
• Oxidative stress

• Parkinson’s disease (PD)
• aconitase 1 (ACO1)
• cystine/glutamate antiporter
• ferroptosis
• iron dysregulation
• iron regulatory protein 1 (IRP1)
• treatment strategy

• Aconitase 1 (ACO1)
• Parkinson’s disease
• baicalein
• iron accumulation
• iron regulatory protein 1 (IRP1)

The iron hormone hepcidin is transcriptionally activated by iron or inflammation via distinct, partially overlapping pathways. We addressed how iron affects inflammatory hepcidin levels and the ensuing hypoferremic response. Dietary iron overload did not mitigate hepcidin induction in lipopolysaccharide (LPS)-treated wild type mice but prevented effective inflammatory hypoferremia. Likewise, LPS modestly decreased serum iron in hepcidin-deficient Hjv^-/- mice, model of hemochromatosis. Synthetic hepcidin triggered hypoferremia in control but not iron-loaded wild type animals. Furthermore, it dramatically decreased hepatic and splenic ferroportin in Hjv^-/- mice on standard or iron-deficient diet, but only triggered hypoferremia in the latter. Mechanistically, iron antagonized hepcidin responsiveness by inactivating IRPs in the liver and spleen to stimulate ferroportin mRNA translation. Prolonged LPS treatment eliminated ferroportin mRNA and permitted hepcidin-mediated hypoferremia in iron-loaded mice. Thus, de novo ferroportin synthesis is a critical determinant of serum iron and finetunes hepcidin-dependent functional outcomes. Our data uncover a crosstalk between hepcidin and IRE/IRP systems that controls tissue ferroportin expression and determines serum iron levels. Moreover, they suggest that hepcidin supplementation therapy is more efficient when combined with iron depletion.

• cell biology
• immunology
• inflammation
• mouse

Compared to cancer cells, macrophages are inert to lipid peroxidation-triggered, iron-dependent cell death known as ferroptosis. Mechanisms underlying macrophage resistance towards ferroptosis are largely obscure. Here, we show that human primary macrophages respond to RSL3, a ferroptosis-inducing inhibitor of glutathione peroxidase 4, by upregulating mRNA expression of the iron transporter ferroportin. RSL3 induces lipid peroxidation, and both, lipid peroxidation as well as ferroportin induction were attenuated by liproxstatin-1, an inhibitor of lipid peroxidation and ferroptosis blocker. At the same time, system x_c^– inhibitor erastin fails to elicit lipid peroxidation or ferroportin expression. Ferroportin induction in response to RSL3 demands nuclear accumulation of the redox-sensitive transcription factor Nrf2 and downregulation of the transcriptional repressor BACH1. Silencing ferroportin or Nrf2 increases the cellular labile iron pool and lipid peroxidation, thereby sensitizing cells towards ferroptosis following RSL3 treatments. In contrast, silencing BACH1 decreases the labile iron pool and lipid peroxidation, enhancing macrophage resistance towards ferroptosis. Our findings reveal Nrf2, BACH1, and ferroportin as important regulators, protecting human macrophages against ferroptosis.

• Antioxidation
• Fetal demise
• Fetal iron supply
• Gestational diabetes mellitus
• Iron homeostasis
• Lipid peroxidation
• Maternal iron status
• Materno-fetal iron transport
• Placental barrier
• Placental ferroptosis
• Preeclampsia

• BACH1
• NFE2L2/NRF2
• cell death
• damage-associated molecular patterns (DAMPs)
• ferroptosis
• lipid peroxidation
• signal transmitter
• transcription factor

Iron is one of the most crucial elements in the human body. In recent years, a kind of programmed, non-apoptotic cell death closely related to iron metabolism-called ferroptosis- has aroused much interest among many scientists. Ferroptosis also interacts with other pathways involved in cell death including iron abnormality, the cystine/glutamate antiporter and lipid peroxidation. Together these pathological pathways exert great impacts on intracerebral hemorrhage (ICH), a lethal cerebrovascular disease with a high incidence rate and mortality rate. Furthermore, the ferroptosis also affects different brain cells (neurons and neuroglial cells) and different organelles (mitochondria and endoplasmic reticulum). Clinical treatments for ferroptosis in ICH have been closely investigated recently. This perspective provides a comprehensive summary of ferroptosis mechanisms after ICH and its interaction with other cell death patterns. Understanding the role of ferroptosis in ICH will open new windows for the future treatments and preventions for ICH and other intracerebral diseases.

• ferroptosis
• intervertebral disc degeneration
• iron
• lipid peroxidation
• therapeutic implication

• Humans
• Ferroptosis
• Intervertebral Disc Degeneration/drug therapy
• Lipid Peroxidation
• Oxidation-Reduction
• Iron

• Iron regulatory element (IRE)
• Iron regulatory proteins (IRPs)
• Neurodegenerative disorders
• Non-iron

• Aging
• C. elegans
• Drosophila
• Homeostasis
• Human diseases
• Iron
• Longevity

• ferritin
• ferroportin
• hemochromatosis
• hemojuvelin
• hepcidin
• iron overload
• next generation sequencing
• transferrin receptor 2

• Adult
• Cation Transport Proteins/genetics
• Child
• Female
• GPI-Linked Proteins/genetics
• Gene-Environment Interaction
• Hemochromatosis Protein/genetics
• Hepcidins/genetics
• High-Throughput Nucleotide Sequencing
• Humans
• Hyperferritinemia/genetics
• Male
• Middle Aged
• Mutation
• Receptors, Transferrin/genetics
• Sequence Analysis, DNA/methods
• Tertiary Care Centers
• Young Adult

• Alzheimer’s disease
• computational biology
• familial Alzheimer’s disease
• gene expression
• iron homeostasis
• iron responsive element
• transcriptomics

• Iron metabolism
• beta-cell function
• diabetes
• reactive oxygen species

• Animals
• Diabetes Mellitus/metabolism
• Homeostasis
• Humans
• Insulin-Secreting Cells/metabolism
• Iron/metabolism
• Models, Biological

• Regione Lombardia Bando F&S Aggregazioni POR FESR 2014-2020
• MIUR Progetto Dipartimenti di Eccellenza. N.D. is supported by Università degli Studi di Milano (Ph.D. fellowship)

• LPS
• Nrf2
• copper
• ferroportin
• macrophages

Iron responsive elements (IREs) are mRNA stem-loop targets for translational control by the two iron regulatory proteins IRP1 and IRP2. They are found in the untranslated regions (UTRs) of genes that code for proteins involved in iron metabolism. There are ten “classic” IRE types that define the conserved secondary and tertiary structure elements necessary for proper IRP binding, and there are 83 published “IRE-like” sequences, most of which depart from the established IRE model. Here are structurally-guided discussions regarding the essential features of an IRE and what is important for IRE family membership.

• covariance model (CM)
• iron regulatory protein (IRP)
• iron-responsive element (IRE)
• messenger RNA (mRNA)
• pseudo-triloop (PTL)
• untranslated region (UTR)

The demand for iron is high in pregnancy to meet the increased requirements for erythropoiesis. Even pregnant females with initially iron‐replete stores develop iron‐deficiency anemia, due to inadequate iron absorption. In anemic females, the maternal iron supply is dedicated to maintaining iron metabolism in the fetus and placenta. Here, using a mouse model of iron deficiency in pregnancy, we show that iron recycled from senescent erythrocytes becomes a predominant source of this microelement that can be transferred to the placenta in females with depleted iron stores. Ferroportin is a key protein in the molecular machinery of cellular iron egress. We demonstrate that under iron deficiency in pregnancy, levels of ferroportin are greatly reduced in the duodenum, placenta and fetal liver, but not in maternal liver macrophages and in the spleen. Although low expression of both maternal and fetal hepcidin predicted ferroportin up‐regulation in examined locations, its final expression level was very likely correlated with tissue iron status. Our results argue that iron released into the circulation of anemic females is taken up by the placenta, as evidenced by high expression of iron importers on syncytiotrophoblasts. Then, a substantial decrease in levels of ferroportin on the basolateral side of syncytiotrophoblasts, may be responsible for the reduced transfer of iron to the fetus. As attested by the lowest decrease in iron content among analyzed tissues, some part is retained in the placenta. These findings confirm the key role played by ferroportin in tuning iron turnover in iron‐deficient pregnant mouse females and their fetuses.

Smith–Lemli–Opitz Syndrome (SLOS) results from mutations in the gene encoding the enzyme DHCR7, which catalyzes conversion of 7-dehydrocholesterol (7DHC) to cholesterol (CHOL). Rats treated with a DHCR7 inhibitor serve as a SLOS animal model, and exhibit progressive photoreceptor-specific cell death, with accumulation of 7DHC and oxidized sterols. To understand the basis of this cell type specificity, we performed transcriptomic analyses on a photoreceptor-derived cell line (661W), treating cells with two 7DHC-derived oxysterols, which accumulate in tissues and bodily fluids of SLOS patients and in the rat SLOS model, as well as with CHOL (negative control), and evaluated differentially expressed genes (DEGs) for each treatment. Gene enrichment analysis and compilation of DEG sets indicated that endoplasmic reticulum stress, oxidative stress, DNA damage and repair, and autophagy were all highly up-regulated pathways in oxysterol-treated cells. Detailed analysis indicated that the two oxysterols exert their effects via different molecular mechanisms. Changes in expression of key genes in highlighted pathways (Hmox1, Ddit3, Trib3, and Herpud1) were validated by immunofluorescence confocal microscopy. The results extend our understanding of the pathobiology of retinal degeneration and SLOS, identifying potential new druggable targets for therapeutic intervention into these and other related orphan diseases.

• Smith–Lemli–Opitz
• cell death
• cell stress
• cholesterol
• gene array
• neurodegeneration
• oxysterol
• photoreceptor

• Ferroportin
• Ferroportin disease
• Hemochromatosis
• Hepcidin
• Iron homeostasis
• Iron metabolism
• Iron transporter

• iron homeostasis
• materno-foetal iron transfer
• piglet anaemia
• swine

Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) have been associated with dysregulation of iron metabolism. The basis for this association is not completely understood. To attempt to investigate this, we studied temporal associations between onset of insulin resistance (IR) and dysregulated iron homeostasis, in a mouse model of T2DM.

Male C57Bl/6 mice (aged 8 weeks) were fed a high-fat diet (HFD; 60% energy from fat) or a control diet (CD; 10% energy from fat) for 4, 8, 12, 16, 20 and 24 weeks. Development of IR was documented, and various metabolic, inflammatory and iron-related parameters were studied in these mice.

HFD-feeding induced weight gain, hepato-steatosis and IR in the mice. Onset of IR occurred from 12 weeks onwards. Hepatic iron stores progressively declined from 16 weeks onwards. Accompanying changes included a decrease in hepatic hepcidin (Hamp1) mRNA expression and serum hepcidin levels and an increase in iron content in the epididymal white adipose tissue (eWAT). Iron content in the liver negatively correlated with that in the eWAT. Factors known to regulate hepatic Hamp1 expression (such as serum iron levels, systemic inflammation, and bone marrow-derived erythroid regulators) were not affected by HFD-feeding. In conclusion, the results show that the onset of IR in HFD-fed mice preceded dysregulation of iron homeostasis, evidence of which were found both in the liver and visceral adipose tissue.

• Adipose tissue iron
• Hepatic iron content
• Hepcidin
• High-fat diet
• Insulin resistance
• Iron

• Anemia
• Chelation
• Heart failure
• Hepcidin
• Iron metabolism
• Mitochondria

Ferroportin (FPN) is the only known cellular iron exporter in mammalian. However, post-transcriptional regulation of intestinal FPN has not yet been completely understood. In this study, bioinformatics algorithms (TargetScan, PicTar, PITA, and miRanda) were applied to predict, screen and obtain microRNA-17 family members (miR-17, miR-20a, miR-20b, and miR-106a) targeting FPN, ‘seed sequence’ and responding binding sites on the 3′untranslated region (3′UTR) region of FPN. Dual-luciferase reporter assays revealed miRNA-17 family members’ mimics decreased the luciferase activity, whereas their inhibitors increased the luciferase activity. Compared with the FPN 3′UTR wild type reporter, co-transfection of a miRNA-17 family members’ over-expression plasmids and FPN 3′UTR mutant reporters enhanced the luciferase activity in HCT116 cells. Transfection with miR-20b overexpression plasmid significantly enhanced its expression, and it inhibited endogenous FPN protein expression in Caco-2 cells. Additionally, tail-vein injection of miR-20b resulted in increasing duodenal miR-20b expression, decreasing duodenal FPN protein expression, which was closely related to lower plasma iron level in mice. Taken together, these data suggest that the miR-20b is identified to regulate intestinal FPN expression in vitro and in vivo, which will provide a potential target for intestinal iron exportation.

• FPN
• miR-20b
• post-transcriptional regulation

• 3' Untranslated Regions
• Animals
• Caco-2 Cells
• Cation Transport Proteins/genetics
• Cation Transport Proteins/metabolism
• Down-Regulation/genetics
• Gene Expression Regulation
• HCT116 Cells
• Humans
• Intestinal Mucosa/metabolism
• Iron/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs/physiology

• SLC40A1
• ferritin
• ferroportin
• hemochromatosis
• iron overload
• non-HFE

• MC_UU_00008/10 Medical Research Council
• MC_UU_12010/10 Medical Research Council

• cancer
• iron regulator proteins
• iron-sulfur cluster biogenesis
• metabolism
• mutant TP53

• Cell Growth Processes/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Homeostasis
• Humans
• Iron/metabolism
• Iron-Regulatory Proteins/metabolism
• Mutation/physiology
• Tumor Suppressor Protein p53/genetics

Recent findings demonstrate that aberrant downregulation of the iron-exporter protein, ferroportin (FPN1), is associated with poor prognosis and osteoclast differentiation in multiple myeloma (MM). Here, we show that FPN1 was downregulated in MM and that clustered regularly interspaced short palindromic repeat (CRISPR)-mediated FPN1 knockout promoted MM cell growth and survival. Using a microRNA target-scan algorithm, we identified miR-17-5p as an FPN1 regulator that promoted cell proliferation and cell cycle progression, and inhibited apoptosis—both in vitro and in vivo. miR-17-5p inhibited retarded tumor growth in a MM xenograft model. Moreover, restoring FPN1 expression at least partially abrogated the biological effects of miR-17-5p in MM cells. The cellular iron concentration regulated the expression of the iron-regulatory protein (IRP) via the 5′-untranslated region of IRP messenger RNA and modulated the post-transcriptional stability of FPN1. Bioinformatics analysis with subsequent chromatin immunoprecipitation-polymerase chain reaction and luciferase activity experiments revealed that the transcription factor Nrf2 drove FPN1 transcription through promoter binding and suppressed miR-17-5p (which also increased FPN1 expression). Nrf2-mediated FPN1 downregulation promoted intracellular iron accumulation and reactive oxygen species. Our study links FPN1 transcriptional and post-transcriptional regulation with MM cell growth and survival, and validates the prognostic value of FPN1 and its utility as a novel therapeutic target in MM.

Myelomonocytic cells are critically involved in iron turnover as aged RBC recyclers. Human monocytes are divided in 3 subpopulations of classical, intermediate, and nonclassical cells, differing in inflammatory and migratory phenotype. Their functions in iron homeostasis are, however, unclear. Here, we asked whether the functional diversity of monocyte subsets translates into differences in handling physiological and pathological iron species. By microarray data analysis and flow cytometry we identified a set of iron-related genes and proteins upregulated in classical and, in part, intermediate monocytes. These included the iron exporter ferroportin (FPN1), ferritin, transferrin receptor, putative transporters of non-transferrin-bound iron (NTBI), and receptors for damaged erythrocytes. Consequently, classical monocytes displayed superior scavenging capabilities of potentially toxic NTBI, which were augmented by blocking iron export via hepcidin. The same subset and, to a lesser extent, the intermediate population, efficiently cleared damaged erythrocytes in vitro and mediated erythrophagocytosis in vivo in healthy volunteers and patients having received blood transfusions. To summarize, our data underline the physiologically important function of the classical and intermediate subset in clearing NTBI and damaged RBCs. As such, these cells may play a nonnegligible role in iron homeostasis and limit iron toxicity in iron overload conditions.

Human classical and intermediate monocytes mediate clearance of non-transferrin-bound iron and erythrophagocytosis.

• Immunology
• Innate immunity
• Metabolism
• Monocytes

• DMT1
• FPN1
• Ferritin
• Hepcidin
• IRPs
• Iron
• TfR1

• Anemia/etiology
• Anemia/metabolism
• Anemia/therapy
• Biological Transport, Active
• Bone Marrow/metabolism
• Cation Transport Proteins/metabolism
• Computational Biology
• Epoetin Alfa/therapeutic use
• Erythrocytes/metabolism
• Erythropoietin/metabolism
• Hepcidins/metabolism
• Humans
• Iron/blood
• Iron/metabolism
• Iron-Dextran Complex/therapeutic use
• Liver/metabolism
• Models, Biological
• Mononuclear Phagocyte System/metabolism
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/metabolism
• Transferrin/metabolism

• Ineffective erythropoiesis
• Red blood cells
• Thalassemia

• Animals
• Biomarkers
• Cell Differentiation
• Erythrocytes/drug effects
• Erythrocytes/metabolism
• Erythropoiesis/drug effects
• Erythropoiesis/genetics
• Hematopoietic Stem Cells/cytology
• Hematopoietic Stem Cells/metabolism
• Humans
• Iron/metabolism
• Molecular Targeted Therapy
• Stress, Physiological
• Thalassemia/blood
• Thalassemia/drug therapy
• Thalassemia/etiology
• Thalassemia/metabolism

• R01 DK090554 NIDDK NIH HHS
• R01 DK095112 NIDDK NIH HHS

• brain
• germinal matrix hemorrhage
• hemorrhage
• iron overload
• iron‐responsive element‐binding protein 2
• neonatal ischemia
• slc4a10

• Animals
• Animals, Newborn
• Behavior, Animal/drug effects
• Cerebral Hemorrhage/genetics
• Cerebral Hemorrhage/metabolism
• Cerebral Hemorrhage/physiopathology
• Cerebral Hemorrhage/therapy
• Cerebrospinal Fluid/metabolism
• Chlorides
• Choroid Plexus/drug effects
• Choroid Plexus/metabolism
• Choroid Plexus/physiopathology
• Cognition/drug effects
• Deferoxamine/pharmacology
• Disease Models, Animal
• Ferric Compounds
• Hydrocephalus/genetics
• Hydrocephalus/metabolism
• Hydrocephalus/physiopathology
• Hydrocephalus/prevention & control
• Injections, Intraventricular
• Iron Regulatory Protein 1/genetics
• Iron Regulatory Protein 1/metabolism
• Iron Regulatory Protein 2/genetics
• Iron Regulatory Protein 2/metabolism
• Motor Activity/drug effects
• RNA, Small Interfering/administration & dosage
• RNAi Therapeutics
• Rats, Sprague-Dawley
• Siderophores/pharmacology
• Sodium-Bicarbonate Symporters/genetics
• Sodium-Bicarbonate Symporters/metabolism

• R01 NS078755 NINDS NIH HHS

Ferroportin Disease (FD) is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of the commonest causes of genetic hyperferritinemia, regardless of ethnicity. FPN1 transfers iron from the intestine, macrophages and placenta into the bloodstream. In FD, loss-of-function mutations of FPN1 limit but do not impair iron export in enterocytes, but they do severely affect iron transfer in macrophages. This leads to progressive and preferential iron trapping in tissue macrophages, reduced iron release to serum transferrin (i.e. inappropriately low transferrin saturation) and a tendency towards anemia at menarche or after intense bloodletting. The hallmark of FD is marked iron accumulation in hepatic Kupffer cells. Numerous FD-associated mutations have been reported worldwide, with a few occurring in different populations and some more commonly reported (e.g. Val192del, A77D, and G80S). FPN1 polymorphisms also represent the gene variants most commonly responsible for hyperferritinemia in Africans. Differential diagnosis includes mainly hereditary hemochromatosis, the syndrome commonly due to either HFE or TfR2, HJV, HAMP, and, in rare instances, FPN1 itself. Here, unlike FD, hyperferritinemia associates with high transferrin saturation, iron-spared macrophages, and progressive parenchymal cell iron load. Abdominal magnetic resonance imaging (MRI), the key non-invasive diagnostic tool for the diagnosis of FD, shows the characteristic iron loading SSL triad (spleen, spine and liver). A non-aggressive phlebotomy regimen is recommended, with careful monitoring of transferrin saturation and hemoglobin due to the risk of anemia. Family screening is mandatory since siblings and offspring have a 50% chance of carrying the pathogenic mutation.

• Fe transporters
• Fe-Zn interaction
• Iron
• Zn transporters
• hepcidin
• zinc