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Metallomics : Integrated Biometal... May 2021Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells... (Review)
Review
Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells forming multimeric assemblies with crystalline iron cores. We discuss the latest findings on ferritin structure and activity and its link to cell metabolism and ferroptosis. The chemistry of iron, including its oxidation states, is important for its biological functions, its reactivity, and the biology of ferritin. Ferritin can be localized in different cellular compartments and secreted by cells with a variety of functions depending on its spatial context. Here, we discuss how cellular ferritin localization is tightly linked to its function in a tissue-specific manner, and how impairment of iron homeostasis is implicated in diseases, including cancer and coronavirus disease 2019. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.
Topics: Biomarkers; Biotechnology; COVID-19; Ceruloplasmin; Drug Delivery Systems; Ferritins; Ferroptosis; Glycosylation; Homeostasis; Humans; Inflammation; Iron; Nanotechnology; Neoplasms; Prognosis; SARS-CoV-2; Tissue Distribution
PubMed: 33881539
DOI: 10.1093/mtomcs/mfab021 -
Blood Reviews May 2009Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine,... (Review)
Review
Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage.
Topics: Apoferritins; Ferritins; Homeostasis; Humans; Iron; Iron Metabolism Disorders; Kininogens; Neoplasms
PubMed: 18835072
DOI: 10.1016/j.blre.2008.08.001 -
Biochimica Et Biophysica Acta Aug 2010Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum... (Review)
Review
BACKGROUND
Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases.
SCOPE OF REVIEW
In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool.
MAJOR CONCLUSIONS
Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer.
GENERAL SIGNIFICANCE
Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights.
Topics: Animals; Biomedical Research; Blood Proteins; Extracellular Space; Ferritins; Health Status; History, 20th Century; History, 21st Century; Humans; Iron Metabolism Disorders
PubMed: 20304033
DOI: 10.1016/j.bbagen.2010.03.011 -
The Journal of Cell Biology Oct 2022A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to...
A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to lysosomes to release iron ions. Two transport pathways have been reported: macroautophagy and ESCRT-dependent endosomal microautophagy. Although the membrane dynamics of these pathways differ, both require NCOA4, which is thought to be an autophagy receptor for ferritin. However, it is unclear whether NCOA4 only acts as an autophagy receptor in ferritin degradation. Here, we found that ferritin particles form liquid-like condensates in a NCOA4-dependent manner. Homodimerization of NCOA4 and interaction between FTH1 and NCOA4 (i.e., multivalent interactions between ferritin particles and NCOA4) were required for the formation of ferritin condensates. Disruption of these interactions impaired ferritin degradation. Time-lapse imaging and three-dimensional correlative light and electron microscopy revealed that these ferritin-NCOA4 condensates were directly engulfed by autophagosomes and endosomes. In contrast, TAX1BP1 was not required for the formation of ferritin-NCOA4 condensates but was required for their incorporation into autophagosomes and endosomes. These results suggest that NCOA4 acts not only as a canonical autophagy receptor but also as a driver to form ferritin condensates to facilitate the degradation of these condensates by macroautophagy (i.e., macroferritinophagy) and endosomal microautophagy (i.e., microferritinophagy).
Topics: Autophagy; Endosomes; Ferritins; Iron; Lysosomes; Nuclear Receptor Coactivators; Phagosomes; Transcription Factors
PubMed: 36066504
DOI: 10.1083/jcb.202203102 -
International Journal of Molecular... Jan 2023Ferritin is a ubiquitous protein that is present in most tissues as a cytosolic protein. The major and common role of ferritin is to bind Fe, oxidize it and sequester it... (Review)
Review
Ferritin is a ubiquitous protein that is present in most tissues as a cytosolic protein. The major and common role of ferritin is to bind Fe, oxidize it and sequester it in a safe form in the cell, and to release iron according to cellular needs. Ferritin is also present at a considerably low proportion in normal mammalian sera and is relatively iron poor compared to tissues. Serum ferritin might provide a useful and convenient method of assessing the status of iron storage, and its measurement has become a routine laboratory test. However, many additional factors, including inflammation, infection, metabolic abnormalities, and malignancy-all of which may elevate serum ferritin-complicate interpretation of this value. Despite this long history of clinical use, fundamental aspects of the biology of serum ferritin are still unclear. According to the high number of factors involved in regulation of ferritin synthesis, secretion, and uptake, and in its central role in iron metabolism, hyperferritinemia is a relatively common finding in clinical practice and is found in a large spectrum of conditions, both genetic and acquired, associated or not with iron overload. The diagnostic strategy to reveal the cause of hyperferritinemia includes family and personal medical history, biochemical and genetic tests, and evaluation of liver iron by direct or indirect methods. This review is focused on the forms of inherited hyperferritinemia with or without iron overload presenting with normal transferrin saturation, as well as a step-by-step approach to distinguish these forms to the acquired forms, common and rare, of isolated hyperferritinemia.
Topics: Humans; Hyperferritinemia; Pedigree; Iron; Iron Overload; Ferritins
PubMed: 36768886
DOI: 10.3390/ijms24032560 -
Journal of Enzyme Inhibition and... Dec 2023In all living organisms, ferritins are a group of proteins important for maintaining iron homeostasis. Increasing amount of studies has shown that recombinant ferritins... (Review)
Review
In all living organisms, ferritins are a group of proteins important for maintaining iron homeostasis. Increasing amount of studies has shown that recombinant ferritins can be widely used in multimodal nanomedicine, especially for anticancer treatment and vaccination. Recombinant particles prepared by fusing viral proteins and ferritin subunits produce a better immune response and higher antibody titres. Moreover, actively-targeted ferritin nanoparticles can recognise receptors and deliver natural or chemical drugs specifically to the tumour tissue. In addition, ferritin-linked or loaded with contrast agents or fluorescent dyes can be used as multimodal particles useful cancer theranostics. In this review, we fully summarised the unitisation of recombinant ferritins in multimodal nanomedicine. The research progress of using recombinant ferritins as nanovaccines, nanozymes, and bioengineered nanocarriers for targeted therapy and bioimaging is emphasised.
Topics: Ferritins; Nanomedicine; Nanoparticles
PubMed: 37263586
DOI: 10.1080/14756366.2023.2219868 -
International Journal of Molecular... Nov 2022The interest in the regulation of iron metabolism has increased in recent years with the clarification of the mechanism by which hepcidin regulates systemic iron...
The interest in the regulation of iron metabolism has increased in recent years with the clarification of the mechanism by which hepcidin regulates systemic iron homeostasis and the discovery of ferritinophagy, the major mechanism of ferritin degradation, which plays a major role in intracellular iron homeostasis and ferroptosis [...].
Topics: Ferritins; Iron; Hepcidins; Homeostasis
PubMed: 36499028
DOI: 10.3390/ijms232314700 -
Experimental & Molecular Medicine Oct 2022The ferritin nanocage is an endogenous protein that exists in almost all mammals. Its hollow spherical structure that naturally stores iron ions has been diversely... (Review)
Review
The ferritin nanocage is an endogenous protein that exists in almost all mammals. Its hollow spherical structure that naturally stores iron ions has been diversely exploited by researchers in biotherapeutics. Ferritin has excellent biosafety profiles, and the nanosized particles exhibit rapid dispersion and controlled/sustained release pharmacokinetics. Moreover, the large surface-to-volume ratio and the disassembly/reassembly behavior of the 24 monomer subunits into a sphere allow diverse modifications by chemical and genetic methods on the surface and inner cage of ferritin. Here, we critically review ferritin and its applications. We (i) introduce the application of ferritin in drug delivery; (ii) present an overview of the use of ferritin in imaging and diagnosis for biomedical purposes; (iii) discuss ferritin-based vaccines; and (iv) review ferritin-based agents currently in clinical trials. Although there are no currently approved drugs based on ferritin, this multifunctional protein scaffold shows immense potential in drug development in diverse categories, and ferritin-based drugs have recently entered phase I clinical trials. This golden shortlist of recent developments will be of immediate benefit and interest to researchers studying ferritin and other protein-based biotherapeutics.
Topics: Animals; Ferritins; Iron; Diagnostic Imaging; Mammals
PubMed: 36192487
DOI: 10.1038/s12276-022-00859-0 -
International Journal of Molecular... May 2023Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic...
Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, = 0.047, respectively) and OS (NR vs. 75.1 months and = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome.
Topics: Humans; Multiple Myeloma; Ferritins; Monoclonal Gammopathy of Undetermined Significance; Bone Marrow; Gene Expression Profiling; Tumor Microenvironment
PubMed: 37240197
DOI: 10.3390/ijms24108852 -
The Israel Medical Association Journal... Jan 2008Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis... (Review)
Review
Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis is regulated by cytokines (tumor necrosis factor-alpha and interleukin-1alpha) at various levels (transcriptional, post-transcriptional, translational) during development, cellular differentiation, proliferation and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes. The immunological actions of ferritin include binding to T lymphocytes, suppression of the delayed-type hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes. Thyroid hormone, insulin and insulin growth factor-1 are involved in the regulation of ferritin at the mRNA level. Ferritin and iron homeostasis are implicated in the pathogenesis of many disorders, including diseases involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections and malignancies, and in systemic lupus erythematosus correlates with disease activity. Some evidence points to the importance of hyperferritinemia in dermatomyositis and multiple sclerosis, but further mechanistic investigations are warranted.
Topics: Autoimmune Diseases; Autoimmunity; Biomarkers; Ferritins; Humans; Infections; Inflammation
PubMed: 18300583
DOI: No ID Found