The cardinal roles of ferroportin and its partners in controlling cellular iron in and out

Yang, Qiuyuan; Liu, Wei; Zhang, Shuping; Liu, Sijin

doi:10.1016/j.lfs.2020.118135

Cited by 26 publications

(17 citation statements)

References 48 publications

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“…In mammalian cells, ferric Fe is transported out of the cytoplasm by an exporter in the plasma membrane called ferroportin [ 138 ], but no homologs for ferroportin have been discovered at this time in D. melanogaster [ 139 ]. Fe is likely transported out of the cytosol and into the ER via dZip13, where it binds to ferritin, and ferritin is then transported out of the cell [ 115 , 139 ].…”

Section: Metal Transport Systems In Drosophila Melanogastermentioning

confidence: 99%

The Effects of Essential and Non-Essential Metal Toxicity in the Drosophila melanogaster Insect Model: A Review

Slobodian

Petahtegoose

Wallis

et al. 2021

Toxics

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The biological effects of environmental metal contamination are important issues in an industrialized, resource-dependent world. Different metals have different roles in biology and can be classified as essential if they are required by a living organism (e.g., as cofactors), or as non-essential metals if they are not. While essential metal ions have been well studied in many eukaryotic species, less is known about the effects of non-essential metals, even though essential and non-essential metals are often chemically similar and can bind to the same biological ligands. Insects are often exposed to a variety of contaminated environments and associated essential and non-essential metal toxicity, but many questions regarding their response to toxicity remain unanswered. Drosophila melanogaster is an excellent insect model species in which to study the effects of toxic metal due to the extensive experimental and genetic resources available for this species. Here, we review the current understanding of the impact of a suite of essential and non-essential metals (Cu, Fe, Zn, Hg, Pb, Cd, and Ni) on the D. melanogaster metal response system, highlighting the knowledge gaps between essential and non-essential metals in D. melanogaster. This review emphasizes the need to use multiple metals, multiple genetic backgrounds, and both sexes in future studies to help guide future research towards better understanding the effects of metal contamination in general.

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Section: Metal Transport Systems In Drosophila Melanogastermentioning

confidence: 99%

The Effects of Essential and Non-Essential Metal Toxicity in the Drosophila melanogaster Insect Model: A Review

Slobodian

Petahtegoose

Wallis

et al. 2021

Toxics

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“…In the circulation, iron in the ferric state (Fe 3+ ) is bound to apo-transferrin, forming holo-transferrin. Both hephaestin and ceruloplasmin influence ferroportin capacity to export ferrous ions into circulation [ 29 ]. Hepcidin, synthesized in the hepatocytes.…”

Section: Iron Deficiencymentioning

confidence: 99%

Anemia in Sports: A Narrative Review

Damian

Vulturar

et al. 2021

Life

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Recent years have brought about new understandings regarding the pathogenesis of anemia in sports. From hemodilution and redistribution considered to contribute to the so-called “sports anemia” to iron deficiency caused by increased demands, dietary restrictions, decreased absorption, increased losses, hemolysis, and sequestration, to genetic determinants of different types of anemia (some related to sport), the anemia in athletes deserves a careful and multifactorial approach. Dietary factors that reduce iron absorption (e.g., phytate, polyphenols) and that augment iron’s bioavailability (e.g., ascorbic acid) should be considered. Celiac disease, more prevalent in female athletes, may underlie an unexplained iron deficiency anemia. Iron loss during exercise occurs in several ways: sweating, hematuria, gastrointestinal bleeding, inflammation, and intravascular and extravascular hemolysis. From a practical point of view, assessing iron status, especially in the athletes at risk for iron deficiency (females, adolescents, in sports with dietary restrictions, etc.), may improve the iron balance and possibly the performance. Hemoglobin and serum ferritin are measures that are easily employable for the evaluation of patients’ iron status. Cutoff values should probably be further assessed with respect to the sex, age, and type of sport. A healthy gut microbiome influences the iron status. Athletes at risk of iron deficiency should perform non-weight-bearing, low-intensity sports to avoid inducing hemolysis.

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“…Although all functions of this protein remain to be documented, the first major roles described in the literature were as a copper transporter, then in iron homeostasis, with its ferroxidase activity, converting ferrous ions [Fe 2+ ] into ferric ions [Fe 3+ ] in the extracellular compartment [ 26 , 28 ]. Interestingly, CP is involved in both iron influx and efflux, respectively allowing capture of ferric ions by transferrin for the transport into the cell, but also facilitating the export activity of ferroportin, with a molecular connection between both proteins, required for iron efflux out of the cell [ 37 , 38 ]. It has been shown in rat astrocytes that CP is predominantly expressed in a form anchored to the membrane with a glycophosphatidylinositol (GPI) and that this form is necessary for the efflux of iron [ 39 ] while another secreted form is predominant in hepatocytes [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

A role for ceruloplasmin in the control of human glioblastoma cell responses to radiation

et al. 2022

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Background Glioblastoma (GB) is the most common and most aggressive malignant brain tumor. In understanding its resistance to conventional treatments, iron metabolism and related pathways may represent a novel avenue. As for many cancer cells, GB cell growth is dependent on iron, which is tightly involved in red-ox reactions related to radiotherapy effectiveness. From new observations indicating an impact of RX radiations on the expression of ceruloplasmin (CP), an important regulator of iron metabolism, the aim of the present work was to study the functional effects of constitutive expression of CP within GB lines in response to beam radiation depending on the oxygen status (21% O2 versus 3% O2). Methods and results After analysis of radiation responses (Hoechst staining, LDH release, Caspase 3 activation) in U251-MG and U87-MG human GB cell lines, described as radiosensitive and radioresistant respectively, the expression of 9 iron partners (TFR1, DMT1, FTH1, FTL, MFRN1, MFRN2, FXN, FPN1, CP) were tested by RTqPCR and western blots at 3 and 8 days following 4 Gy irradiation. Among those, only CP was significantly downregulated, both at transcript and protein levels in the two lines, with however, a weaker effect in the U87-MG, observable at 3% O2. To investigate specific role of CP in GB radioresistance, U251-MG and U87-MG cells were modified genetically to obtain CP depleted and overexpressing cells, respectively. Manipulation of CP expression in GB lines demonstrated impact both on cell survival and on activation of DNA repair/damage machinery (γH2AX); specifically high levels of CP led to increased production of reactive oxygen species, as shown by elevated levels of superoxide anion, SOD1 synthesis and cellular Fe2 + . Conclusions Taken together, these in vitro results indicate for the first time that CP plays a positive role in the efficiency of radiotherapy on GB cells.

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The cardinal roles of ferroportin and its partners in controlling cellular iron in and out

Cited by 26 publications

References 48 publications

The Effects of Essential and Non-Essential Metal Toxicity in the Drosophila melanogaster Insect Model: A Review

The Effects of Essential and Non-Essential Metal Toxicity in the Drosophila melanogaster Insect Model: A Review

Anemia in Sports: A Narrative Review

A role for ceruloplasmin in the control of human glioblastoma cell responses to radiation

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