scholarly journals FTH1 Pseudogenes in Cancer and Cell Metabolism

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2554
Author(s):  
Maddalena Di Sanzo ◽  
Barbara Quaresima ◽  
Flavia Biamonte ◽  
Camillo Palmieri ◽  
Maria Concetta Faniello
Keyword(s):  
Gene Expression ◽  
Cell Metabolism ◽  
Structural Features ◽  
Intracellular Iron ◽  
Iron Storage ◽  
Master Regulators ◽  
Detailed Classification ◽  
Ferritin Gene ◽  
Complex Regulatory Network ◽  
Iron Storage Protein

Ferritin, the principal intracellular iron-storage protein localized in the cytoplasm, nucleus, and mitochondria, plays a major role in iron metabolism. The encoding ferritin genes are members of a multigene family that includes some pseudogenes. Even though pseudogenes have been initially considered as relics of ancient genes or junk DNA devoid of function, their role in controlling gene expression in normal and transformed cells has recently been re-evaluated. Numerous studies have revealed that some pseudogenes compete with their parental gene for binding to the microRNAs (miRNAs), while others generate small interference RNAs (siRNAs) to decrease functional gene expression, and still others encode functional mutated proteins. Consequently, pseudogenes can be considered as actual master regulators of numerous biological processes. Here, we provide a detailed classification and description of the structural features of the ferritin pseudogenes known to date and review the recent evidence on their mutual interrelation within the complex regulatory network of the ferritin gene family.

scholarly journals Adipose Tissue Expansion by Overfeeding Healthy Men Alters Iron Gene Expression

2018 ◽  
Vol 104 (3) ◽  
pp. 688-696 ◽  
Author(s):  
Berenice Segrestin ◽  
José Maria Moreno-Navarrete ◽  
Kevin Seyssel ◽  
Maud Alligier ◽  
Emmanuelle Meugnier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Serum Iron ◽  
Tissue Expansion ◽  
Lipid Storage ◽  
Mrna Levels ◽  
Intracellular Iron ◽  
Gene Encoding ◽  
Iron Storage ◽  
Healthy Men

Abstract Context Iron overload has been associated with greater adipose tissue (AT) depots. We retrospectively studied the potential interactions between iron and AT during an experimental overfeeding in participants without obesity. Methods Twenty-six participants (mean body mass index ± SD, 24.7 ± 3.1 kg/m2) underwent a 56-day overfeeding (+760 kcal/d). Serum iron biomarkers (ELISA), subcutaneous AT (SAT) gene expression, and abdominal AT distribution assessed by MRI were analyzed at the beginning and the end of the intervention. Results Before intervention: SAT mRNA expression of the iron transporter transferrin (Tf) was positively correlated with the expression of genes related to lipogenesis (lipin 1, ACSL1) and lipid storage (SCD). SAT expression of the ferritin light chain (FTL) gene, encoding ferritin (FT), an intracellular iron storage protein, was negatively correlated to SREBF1, a gene related to lipogenesis. Serum FT (mean, 92 ± 57 ng/mL) was negatively correlated with the expression of SAT genes linked to lipid storage (SCD, DGAT2) and to lipogenesis (SREBF1, ACSL1). After intervention: Overfeeding led to a 2.3 ± 1.3-kg weight gain. In parallel to increased expression of lipid storage–related genes (mitoNEET, SCD, DGAT2, SREBF1), SAT Tf, SLC40A1 (encoding ferroportin 1, a membrane iron export channel) and hephaestin mRNA levels increased, whereas SAT FTL mRNA decreased, suggesting increased AT iron requirement. Serum FT decreased to 67 ± 43 ng/mL. However, no significant associations between serum iron biomarkers and AT distribution or expansion were observed. Conclusion In healthy men, iron metabolism gene expression in SAT is associated with lipid storage and lipogenesis genes expression and is modulated during a 56-day overfeeding diet.

scholarly journals Iron storage capacities and associated ferritin gene expression among marine diatoms

2018 ◽  
Vol 63 (4) ◽  
pp. 1677-1691 ◽  
Author(s):  
Natalie R. Cohen ◽  
Elizabeth Mann ◽  
Brooke Stemple ◽  
Carly M. Moreno ◽  
Sara Rauschenberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Marine Diatoms ◽  
Iron Storage ◽  
Ferritin Gene

scholarly journals Mobilization of Iron Stored in Bacterioferritin Is Required for Metabolic Homeostasis in Pseudomonas aeruginosa

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 980
Author(s):  
Achala N. D. Punchi Hewage ◽  
Leo Fontenot ◽  
Jessie Guidry ◽  
Thomas Weldeghiorghis ◽  
Anil K. Mehta ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Culture Media ◽  
Acid Synthesis ◽  
Iron Limitation ◽  
Metabolic Homeostasis ◽  
Intracellular Iron ◽  
Amino Acid Synthesis ◽  
Iron Storage ◽  
Low Levels ◽  
Iron Storage Protein

Iron homeostasis offers a significant bacterial vulnerability because pathogens obtain essential iron from their mammalian hosts, but host-defenses maintain vanishingly low levels of free iron. Although pathogens have evolved mechanisms to procure host-iron, these depend on well-regulated iron homeostasis. To disrupt iron homeostasis, our work has targeted iron mobilization from the iron storage protein bacterioferritin (BfrB) by blocking a required interaction with its cognate ferredoxin partner (Bfd). The blockade of the BfrB–Bfd complex by deletion of the bfd gene (Δbfd) causes iron to irreversibly accumulate in BfrB. In this study we used mass spectrometry and NMR spectroscopy to compare the proteomic response and the levels of key intracellular metabolites between wild type (wt) and isogenic ΔbfdP. aeruginosa strains. We find that the irreversible accumulation of unusable iron in BfrB leads to acute intracellular iron limitation, even if the culture media is iron-sufficient. Importantly, the iron limitation and concomitant iron metabolism dysregulation trigger a cascade of events that lead to broader metabolic homeostasis disruption, which includes sulfur limitation, phenazine-mediated oxidative stress, suboptimal amino acid synthesis and altered carbon metabolism.

scholarly journals Influence of Extracellular Vesicles Isolated From Osteoblasts of Patients With Cox-Arthrosis and/or Osteoporosis on Metabolism and Osteogenic Differentiation of BMSCs

2020 ◽  
Vol 8 ◽  
Author(s):  
Tanja Niedermair ◽  
Christoph Lukas ◽  
Shushan Li ◽  
Sabine Stöckl ◽  
Benjamin Craiovan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Osteogenic Differentiation ◽  
Extracellular Vesicles ◽  
Bone Structure ◽  
Cell Metabolism ◽  
Marker Gene ◽  
Structural Features ◽  
Alizarin Red ◽  
The Impact ◽  
Stimulation Of

Background: Studies with extracellular vesicles (EVs), including exosomes, isolated from mesenchymal stem cells (MSC) indicate benefits for the treatment of musculoskeletal pathologies as osteoarthritis (OA) and osteoporosis (OP). However, little is known about intercellular effects of EVs derived from pathologically altered cells that might influence the outcome by counteracting effects from “healthy” MSC derived EVs. We hypothesize, that EVs isolated from osteoblasts of patients with hip OA (coxarthrosis/CA), osteoporosis (OP), or a combination of both (CA/OP) might negatively affect metabolism and osteogenic differentiation of bone-marrow derived (B)MSCs.Methods: Osteoblasts, isolated from bone explants of CA, OP, and CA/OP patients, were compared regarding growth, viability, and osteogenic differentiation capacity. Structural features of bone explants were analyzed via μCT. EVs were isolated from supernatant of naïve BMSCs and CA, OP, and CA/OP osteoblasts (osteogenic culture for 35 days). BMSC cultures were stimulated with EVs and subsequently, cell metabolism, osteogenic marker gene expression, and osteogenic differentiation were analyzed.Results: Trabecular bone structure was different between the three groups with lowest number and highest separation in the CA/OP group. Viability and Alizarin red staining increased over culture time in CA/OP osteoblasts whereas growth of osteoblasts was comparable. Alizarin red staining was by trend higher in CA compared to OP osteoblasts after 35 days and ALP activity was higher after 28 and 35 days. Stimulation of BMSC cultures with CA, OP, and CA/OP EVs did not affect proliferation but increased caspase 3/7-activity compared to unstimulated BMSCs. BMSC viability was reduced after stimulation with CA and CA/OP EVs compared to unstimulated BMSCs or stimulation with OP EVs. ALP gene expression and activity were reduced in BMSCs after stimulation with CA, OP, and CA/OP EVs. Stimulation of BMSCs with CA EVs reduced Alizarin Red staining by trend.Conclusion: Stimulation of BMSCs with EVs isolated from CA, OP, and CA/OP osteoblasts had mostly catabolic effects on cell metabolism and osteogenic differentiation irrespective of donor pathology and reflect the impact of tissue microenvironment on cell metabolism. These catabolic effects are important for understanding differences in effects of EVs on target tissues/cells when harnessing them as therapeutic drugs.

scholarly journals Chemistry and Biology of Ferritin

Metallomics ◽  
2021 ◽  
Author(s):  
Marina Plays ◽  
Sebastian Müller ◽  
Raphaël Rodriguez
Keyword(s):  
Iron Homeostasis ◽  
Cell Metabolism ◽  
Essential Element ◽  
Biological Functions ◽  
Iron Storage ◽  
Potential Biomarker ◽  
Specific Manner ◽  
Cellular Compartments ◽  
Structure And Activity ◽  
Iron Storage Protein

Abstract 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 oxidations 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 COVID-19. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.

scholarly journals Differential Role of Ferritins in Iron Metabolism and Virulence of the Plant-Pathogenic Bacterium Erwinia chrysanthemi 3937

2007 ◽  
Vol 190 (5) ◽  
pp. 1518-1530 ◽  
Author(s):  
Aïda Boughammoura ◽  
Berthold F. Matzanke ◽  
Lars Böttger ◽  
Sylvie Reverchon ◽  
Emmanuel Lesuisse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Iron Homeostasis ◽  
Reverse Genetics ◽  
Bacterial Species ◽  
Erwinia Chrysanthemi ◽  
Intermediate Phenotype ◽  
Redox Stress ◽  
Intracellular Iron ◽  
Iron Storage

ABSTRACT During infection, the phytopathogenic enterobacterium Erwinia chrysanthemi has to cope with iron-limiting conditions and the production of reactive oxygen species by plant cells. Previous studies have shown that a tight control of the bacterial intracellular iron content is necessary for full virulence. The E. chrysanthemi genome possesses two loci that could be devoted to iron storage: the bfr gene, encoding a heme-containing bacterioferritin, and the ftnA gene, coding for a paradigmatic ferritin. To assess the role of these proteins in the physiology of this pathogen, we constructed ferritin-deficient mutants by reverse genetics. Unlike the bfr mutant, the ftnA mutant had increased sensitivity to iron deficiency and to redox stress conditions. Interestingly, the bfr ftnA mutant displayed an intermediate phenotype for sensitivity to these stresses. Whole-cell analysis by Mössbauer spectroscopy showed that the main iron storage protein is FtnA and that there is an increase in the ferrous iron/ferric iron ratio in the ftnA and bfr ftnA mutants. We found that ftnA gene expression is positively controlled by iron and the transcriptional repressor Fur via the small antisense RNA RyhB. bfr gene expression is induced at the stationary phase of growth. The σS transcriptional factor is necessary for this control. Pathogenicity tests showed that FtnA and the Bfr contribute differentially to the virulence of E. chrysanthemi depending on the host, indicating the importance of a perfect control of iron homeostasis in this bacterial species during infection.

Recombinant ferritin protects mice against challenge with Echinococcus granulosus ?

2009 ◽  
Vol 54 (4) ◽  
Author(s):  
Yana Wang ◽  
Zongji Li ◽  
Zhaoyu Li ◽  
Yang Bo ◽  
Wei Zhao
Keyword(s):  
Echinococcus Granulosus ◽  
Protective Efficacy ◽  
Effective Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Intracellular Iron ◽  
Promising Candidate ◽  
Iron Storage ◽  
Iron Storage Protein

AbstractFerritin is well known as the main intracellular iron storage protein in both prokaryotes and eukaryotes, keeping it in a soluble and non-toxic form, though the role of ferritin as a vaccine candidate in echinococcosis has not yet been delineated. Through our study, ferritin was cloned from Echinococcus granulosus and expressed in Escherichia coli. The recombinant E. granulosus ferritin (rEgferritin) has a molecular weight of 19 kDa and could be recognized by anti-mice serum in Western blotting. The specific antibody was detected by enzyme-linked immunosorbent assay. Mice vaccinated with rEgferritin and challenged intraperitoneally with E. granulosus protoscoleces revealed significant protective efficacy up to 85.6%, compared with the control group. Thus, rEgferritin could be a promising candidate as an effective vaccine to prevent the infection of echinococcosis.

Polygonal profiles of ferritin molecules

1983 ◽  
Vol 41 ◽  
pp. 600-601
Author(s):  
William H. Massover
Keyword(s):  
Axial Ratio ◽  
X Ray Diffraction ◽  
Rhombic Dodecahedron ◽  
Apparent Contradiction ◽  
Iron Storage ◽  
X Ray ◽  
Hexagonal Shape ◽  
Axes Of Symmetry ◽  
Apparent Conflict ◽  
Iron Storage Protein

The molecular structure of the iron-storage protein, ferritin, is becoming known in ever finer detail. The 24 apoferritin subunits (MW ca. 20,000) have a 2:1 axial ratio and are polymerized with 4:3:2 symmetry to form an outer shell surrounding a variable amount of microcrystalline iron, Recent x-ray diffraction results indicate that the projected outline of the native molecule has a quasi-hexagonal shape when viewed down the 3-fold axes of symmetry, and a quasi-square shape when looking down the 4-fold axes. To date, no electron microscope study has reported observing anything other than circular profiles, which would indicate that ferritin is strictly spherical. The apparent conflict between the "hollow sphere" of electron microscopy (E.M.) and the "truncated rhombic dodecahedron" of x-ray diffraction could reflect the poorer effective resolution of E.M. coming from radiation damage, staining, drying, etc. The present study investigates the detailed shape of individual ferritin molecules in order to search for the predicted aspherical profiles and to interpret the nature of this apparent contradiction.

Iron storage sites in the myocardium as revealed by cytohistochemistry

1988 ◽  
Vol 46 ◽  
pp. 394-395
Author(s):  
M. Ashraf ◽  
F. Thompson ◽  
S. Miki ◽  
P. Srivastava
Keyword(s):  
Cardiac Tissue ◽  
Coronary Perfusion ◽  
Intracellular Iron ◽  
Ether Anesthesia ◽  
Intense Staining ◽  
Iron Storage ◽  
Thin Sections ◽  
Rat Hearts ◽  
Cacodylate Buffer ◽  
Made In

Iron is believed to play an important role in the pathogenesis of ischemic injury. However, the sources of intracellular iron in myocytes are not yet defined. In this study we have attempted to localize iron at various cellular sites of the cardiac tissue with the ferrocyanide technique.Rat hearts were excised under ether anesthesia. They were fixed with coronary perfusion with 3% buffered glutaraldehyde made in 0.1 M cacodylate buffer pH 7.3. Sections, 60 μm in thickness, were cut on a vibratome and were incubated in the medium containing 500 mg of potassium ferrocyanide in 49.5 ml H2O and 0.5 ml concentrated HC1 for 30 minutes at room temperature. Following rinses in the buffer, tissues were dehydrated in ethanol and embedded in Spurr medium.The examination of thin sections revealed intense staining or reaction product in peroxisomes (Fig. 1).

Post-Transcriptional Regulation of Cardiac Sarcomere Protein Titin Through 3’ Untranslated Regions

2013 ◽  
Vol 9 ◽  
Author(s):  
Tara A Shrout
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Striated Muscle ◽  
Binding Capacity ◽  
Structural Features ◽  
Neonatal Rat ◽  
Regulatory Control ◽  
Untranslated Regions ◽  
Luciferase Reporter ◽  
Regulatory Effects

Titin is the largest known protein in the human body, and forms the backbone of all striated muscle sarcomeres. The elastic nature of titin is an important component of muscle compliance and functionality. A significant amount of energy is expended to synthesize titin, thus we postulate that titin gene expression is under strict regulatory control in order to conserve cellular resources. In general, gene expression is mediated in part by post-transcriptional control elements located within the 5’ and 3’ untranslated regions (UTRs) of mature mRNA. The 3’UTR in particular contains structural features that affect binding capacity to other RNA components, such as MicroRNA, which control mRNA localization, translation, and degradation. The degree and significance of the regulatory effects mediated by two determined variants of titin’s 3’ UTR were evaluated in Neonatal Rat Ventricular Myocyte and Human Embryonic Kidney cell lines. Recombinant plasmids to transfect these cells lines were engineered by insertion of the variant titin 3’UTR 431- and 1047-base pairs sequences into luciferase reporter vectors. Expression due to an unaltered reporter vector served as the control. Quantitative changes in luciferase activity due to the recombinants proportionally represented the effect titin’s respective 3’UTR conferred on downstream post-transcriptional expression relative to the control. The effect due to titin’s shorter 3’UTR sequence was inconclusive; however, results illustrated that titin’s longer 3’UTR sequence caused a 35 percent decrease in protein expression. Secondary structural analysis of the two sequences revealed differential folding patterns that affect the stability and degree of MicroRNA-binding within titin’s variant 3’UTR sequences.

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