Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Knutson, Mitchell D.

doi:10.1074/jbc.r117.786632

Cited by 110 publications

(84 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The daily production of 200 billion new erythrocytes within the human bone marrow requires an efficient iron trafficking system to ensure optimal heme biosynthesis. 3 The high demand for iron in developing erythrocytes is primarily fulfilled by splenic and hepatic macrophages that recycle senescent erythrocytes. 4,5 Dietary iron can also enter the circulation via the gastrointestinal tract, 6,7 and iron can be mobilized from ferritin storage within the liver.…”

Section: Iron In Biologymentioning

confidence: 99%

Intracellular iron and heme trafficking and metabolism in developing erythroblasts

Kafina

Paw

2017

Metallomics

View full text Add to dashboard Cite

Vertebrate red blood cells (RBCs) arise from erythroblasts in the human bone marrow through a process known as erythropoiesis. Iron uptake is a crucial hallmark, essential for heme biosynthesis in the differentiating erythroblasts, which are dedicated to producing hemoglobin. Erythropoiesis is facilitated by a network of intracellular transport proteins, chaperones, and circulating hormones. Intracellular iron is targeted to the mitochondria for incorporation into a porphyrin ring to form heme and cytosolic iron-sulfur proteins, including Iron Regulatory Protein 1 (IRP1). These processes are tightly regulated to prevent both excess and insufficient levels of iron and heme precursors. Crosstalk between the heme and iron-sulfur synthesizing pathways has been demonstrated to serve as a regulatory feedback mechanism. The activity of δ-aminolevulinic acid synthase (ALAS), the first and rate-limiting enzyme of heme biosynthesis, is a fundamental node of this regulation. Recently, the mitochondrial unfoldase, ClpX, has received attention as a novel key player that modulates this step in heme biogenesis, implicating a role in the pathophysiology of anemic diseases. This chapter reviews the canonical pathways in intracellular iron and heme trafficking and recent findings of iron and heme metabolism in vertebrate red cells. A discussion of the molecular approaches to studying iron and heme transport is provided to highlight opportunities for revealing therapeutic targets.

show abstract

Section: Iron In Biologymentioning

confidence: 99%

Intracellular iron and heme trafficking and metabolism in developing erythroblasts

Kafina

Paw

2017

Metallomics

View full text Add to dashboard Cite

show abstract

“…Cluster CM0 had the highest level of expression of inflammatory genes including TNF, S100A8, S100A9, NFKB1 and the Wnt pathway activator TCF7L2. By contrast, CM4 expressed many genes associated with alternatively activated macrophages, including CD163 and SLC40A1 (ferroportin), which control iron homeostasis 13 . CM4 also abundantly expressed IGF1 and DAB2, both drivers of the alternatively activated phenotype 14,15 and folate receptor beta (FOLR2), a receptor expressed .…”

Section: Classification and Annotation Of Myeloid Cell Clusters Reveamentioning

confidence: 99%

The immune cell landscape in kidneys of lupus nephritis patients

Arazi

Rao

Berthier

et al. 2018

Preprint

View full text Add to dashboard Cite

Lupus nephritis is a potentially fatal autoimmune disease, whose current treatment is ineffective and often toxic. To gain insights into disease mechanisms, we analyzed kidney samples from lupus nephritis patients and healthy controls using single-cell RNA-seq. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid, T, NK and B cells, demonstrating both pro-inflammatory and resolving responses. We found evidence of local activation of B cells correlated with an age-associated B cell signature, and of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, pointing to potential therapeutic targets. Gene expression of immune cells in urine and kidney was highly correlated, suggesting urine may be a surrogate for kidney biopsies. Our results provide a first comprehensive view of the complex network of leukocytes active in lupus nephritis kidneys.

show abstract

“…10 Therefore, biological systems must control iron metabolism by providing the adequate amount of iron for proper cellular function while limiting iron toxicity. 11,12 Iron has also a role in pathogen virulence. The growth of microbial pathogens within the host usually requires iron as an essential nutrient.…”

Section: Introductionmentioning

confidence: 99%

The human iron-proteome†

et al. 2018

View full text Add to dashboard Cite

Organisms from all kingdoms of life use iron-proteins in a multitude of functional processes. We applied a bioinformatics approach to investigate the human portfolio of iron-proteins. We separated ironproteins based on the chemical nature of their metal-containing cofactors: individual iron ions, heme cofactors and iron-sulfur clusters. We found that about 2% of human genes encode an iron-protein.Of these, 35% are proteins binding individual iron ions, 48% are heme-binding proteins and 17% are iron-sulfur proteins. More than half of the human iron-proteins have a catalytic function. Indeed, we predict that 6.5% of all human enzymes are iron-dependent. This percentage is quite different for the various enzyme classes. Human oxidoreductases feature the largest fraction of iron-dependent family members (about 37%). The distribution of iron proteins in the various cellular compartments is uneven.In particular, the mitochondrion and the endoplasmic reticulum are enriched in iron-proteins with respect to the average content of the cell. Finally, we observed that genes encoding iron-proteins are more frequently associated to pathologies than the all other human genes on average. The present research provides an extensive overview of iron usage by the human proteome, and highlights several specific features of the physiological role of iron ions in human cells. Significance to metallomicsIron is one of the most ancient and abundant metal ions in living organisms: it participates in fundamental biological processes, such as photosynthesis, and respiration. It is an essential metal ion for humans. Here, we applied a bioinformatics approach to predict the entire set of human proteins that use iron as cofactor. We found that about 2% of human genes encode an iron-protein. In particular, 35% are proteins binding individual iron ions, 48% are heme-binding proteins and 17% are iron-sulfur proteins. Most of these proteins are enzymes: 37% of the human oxidoreductases need an iron ion to perform their catalytic mechanisms. The analysis of the subcellular location highlighted that some organelles are enriched in iron-proteins, in particular about 7% of the proteins localized in the endoplasmic reticulum and in the mitochondrion bind iron. Finally, our data show that mutations in genes encoding iron-binding proteins are more likely to be associated with pathology than all human genes on average.

show abstract

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Cited by 110 publications

References 99 publications

Intracellular iron and heme trafficking and metabolism in developing erythroblasts

Intracellular iron and heme trafficking and metabolism in developing erythroblasts

The immune cell landscape in kidneys of lupus nephritis patients

The human iron-proteome†

Contact Info

Product

Resources

About