Ferritin as a Cytosol Iron Transport Intermediate in Human Reticulocytes

Speyer, Barbara E.; Fielding, J.

doi:10.1111/j.1365-2141.1979.tb01130.x

Cited by 51 publications

(19 citation statements)

References 26 publications

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“…This supports the theory that ferritin is not merely an iron-storage molecule, but it can act as an intermediate in iron transport (Speyer and Fielding, 1979). Currently, little is understood regarding the physiological mechanisms of ferritin-iron mobilization.…”

supporting

confidence: 59%

Examination of the Mechanism(s) Involved in Doxorubicin-Mediated Iron Accumulation in Ferritin: Studies Using Metabolic Inhibitors, Protein Synthesis Inhibitors, and Lysosomotropic Agents

Kwok¹,

Richardson²

2004

Mol Pharmacol

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Anthracyclines are potent anticancer agents, but their use is limited by cardiotoxicity at high cumulative doses. The mechanisms involved in anthracycline-mediated cardiotoxicity are still poorly understood, but numerous investigations have indicated a role for iron in this process. Our previous studies using neoplastic and myocardial cells showed that anthracyclines inhibit iron mobilization from the iron storage protein, ferritin, resulting in marked accumulation of ferritin-iron. Although the process of ferritin-iron mobilization is little understood, catabolism of ferritin by lysosomes may be a likely mechanism.

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supporting

confidence: 59%

Examination of the Mechanism(s) Involved in Doxorubicin-Mediated Iron Accumulation in Ferritin: Studies Using Metabolic Inhibitors, Protein Synthesis Inhibitors, and Lysosomotropic Agents

Kwok¹,

Richardson²

2004

Mol Pharmacol

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“…As the roles of the H-subunit and L-subunit differ in the mineralization process, the subunit composition of ferritin will influence the metabolic properties of the assembled ferritin molecules (Harrison & Arosio, 1996;Levi et al, 1994). H-subunit rich ferritins have been shown to accumulate and release iron faster than do L-subunit rich ferritins Chiancone & Stefanini, 1984;Wagstaff et al, 1982;Worwood, 1990) and it is suggested that the H-subunit rich ferritins permit more dynamic in-tracellular traffic of iron (Chiancone & Stefanini, 1984;Speyer & Fielding, 1979). L-subunit rich ferritins apparently contain more iron than those ferritins rich in H-subunits (Bomford et al, 1981;Chiancone & Stefanini, 1984) and there are indications that the L-subunit rich ferritins predominate in cell types that play a role in the storage of iron (Boyd et al, 1985;Chiancone & Stefanini, 1984;Coccia et al, 1992;Powell et al, 1975).…”

Section: Isoferritins Different H-subunit/l-subunit Compositions Of Tmentioning

confidence: 99%

Ferritin and ferritin isoforms I: Structure–function relationships, synthesis, degradation and secretion

Koorts

Viljoen

2007

Archives of Physiology and Biochemistry

134

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Ferritin is the intracellular protein responsible for the sequestration, storage and release of iron. Ferritin can accumulate up to 4500 iron atoms as a ferrihydrite mineral in a protein shell and releases these iron atoms when there is an increase in the cell's need for bioavailable iron. The ferritin protein shell consists of 24 protein subunits of two types, the H-subunit and the L-subunit. These ferritin subunits perform different functions in the mineralization process of iron. The ferritin protein shell can exist as various combinations of these two subunit types, giving rise to heteropolymers or isoferritins. Isoferritins are functionally distinct and characteristic populations of isoferritins are found depending on the type of cell, the proliferation status of the cell and the presence of disease. The synthesis of ferritin is regulated both transcriptionally and translationally. Translation of ferritin subunit mRNA is increased or decreased, depending on the labile iron pool and is controlled by an ironresponsive element present in the 5'-untranslated region of the ferritin subunit mRNA. The transcription of the genes for the ferritin subunits is controlled by hormones and cytokines, which can result in a change in the pool of translatable mRNA. The levels of intracellular ferritin are determined by the balance between synthesis and degradation. Degradation of ferritin in the cytosol results in complete release of iron, while degradation in secondary lysosomes results in the formation of haemosiderin and protection against iron toxicity. The majority of ferritin is found in the cytosol. However, ferritin with slightly different properties can also be found in organelles such as nuclei and mitochondria. Most of the ferritin produced intracellularly is harnessed for the regulation of iron bioavailability; however, some of the ferritin is secreted and internalized by other cells. In addition to the regulation of iron bioavailability ferritin may contribute to the control of myelopoiesis and immunological responses.

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“…Although various studies indicate that H-subunit-rich ferritins are more suitable for protecting against oxidative damage, both H-and L-subunitrich ferritins have been shown to reduce the accumulation of ROS. 28 However, H-subunitrich ferritins accumulate and release iron faster than L-subunit-rich ferritins, 14,15,29,30 and it is suggested that the H-subunit-rich ferritins permit more dynamic intracellular traffic of iron, 15,31 while L-subunit-rich ferritins can accumulate more iron, 15,32 and retain iron more firmly than their H-subunit-rich counterparts. 33 It is thus feasible to accept that the increase in the H-and L-subunits of ferritin in osteoarthritis would be to sequester bioavailable iron and to protect against the unwarranted production of ROS.…”

Section: Discussionmentioning

confidence: 99%

Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

Koorts

Levay

Hall

et al. 2012

Exp Biol Med (Maywood)

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Osteoarthritis is a disease characterized by an increase in the production of reactive oxygen species (ROS) in afflicted joints. Excess iron, due to its role in the production of ROS and crystal deposition in the joints, is implicated in the disease progression of osteoarthritis. Ferritin is a major regulator of the bioavailability of iron, and its functions are determined largely by the combination of H- and L-subunits present in its outer protein shell. The purpose of the study was to investigate the expression of the H- and L-subunits of ferritin in bone marrow macrophages of osteoarthritis patients. The cytokine profiles were assessed as cytokines play an important role in the expression of the ferritin subunits. The H-subunit of ferritin in the bone marrow macrophages was significantly higher ( P value = 0.035) in the osteoarthritis patients compared with the controls (107.84; 69.25–167.94 counts/ μm2; n= 7 versus 71.07; 58.56–86.26 counts/ μm2; n= 19). A marginally significant increase ( P value = 0.059) was shown for the expression of the L-subunit in the osteoarthritis patients compared with the controls (133.03; 104.04–170.10 counts/ μm2; n= 7 versus 104.23; 91.53–118.70 counts/ μm2; n= 19). The osteoarthritis and control groups had comparable C-reactive protein, as well as proinflammatory and anti-inflammatory cytokine concentrations. The major exception was for transforming growth factor- β (TGF- β), which was higher ( P value = 0.014) in the plasma of the osteoarthritis patients (16.69; 13.09–21.28 ng/mL; n= 7 versus 8.60; 6.34–11.67 ng/mL; n= 19). Up-regulation of the ferritin subunits decreases the levels of bioavailable iron and provides protection against the unwarranted production of ROS and crystal deposition. A role for TGF- β in the up-regulation of the expression of the H-subunit, and possibly the L-subunit, of ferritin is postulated in osteoarthritis.

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Ferritin as a Cytosol Iron Transport Intermediate in Human Reticulocytes

Cited by 51 publications

References 26 publications

Examination of the Mechanism(s) Involved in Doxorubicin-Mediated Iron Accumulation in Ferritin: Studies Using Metabolic Inhibitors, Protein Synthesis Inhibitors, and Lysosomotropic Agents

Examination of the Mechanism(s) Involved in Doxorubicin-Mediated Iron Accumulation in Ferritin: Studies Using Metabolic Inhibitors, Protein Synthesis Inhibitors, and Lysosomotropic Agents

Ferritin and ferritin isoforms I: Structure–function relationships, synthesis, degradation and secretion

Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

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