Ferritin iron deposition and mobilisation

Crichton, Robert R.; Roman, Françoise; Roland, Francine; Pâques, Eric-P.; Pâques, Anne-Thérèse; Vandamme, Erick

doi:10.1016/0304-5102(80)85024-3

Cited by 24 publications

(13 citation statements)

References 19 publications

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“…A contribution to the rate from reoxidation of Fe 2ϩ to Fe 3ϩ is suggested by the lag. Only 10% of the Fe could be chelated by DFO in the absence of urea, which corresponds to earlier data obtained with horse spleen ferritin (26), whereas when the pore was open as in H-L134P, 39% of the Fe mineral could be removed with DFO. Fe removal rates from ferritin apparently depend much more on the state of the pores than on the type of chelator or the oxidation state of the Fe-chelator complex (Table 2).…”

supporting

confidence: 70%

“…DFO is thought to trap Fe 2ϩ during intracellular transfer into and out of ferritin because of the reducing environment in cells, and the more stable Fe 3ϩ -DFO forms as oxygen is available. DFO alone removes little Fe from ferritin in solution (26). To determine whether unfolding ferritin pores increased DFO chelation of ferritin Fe, the chelator was substituted for bipyridyl in the aerobic solutions of NADH͞FMN used in the previous experiments ( Fig.…”

mentioning

confidence: 99%

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Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral

Liu¹,

Jin²,

Theil³

2003

Proc. Natl. Acad. Sci. U.S.A.

193

245

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Iron is concentrated in ferritin, a spherical protein with a capacious cavity for ferric nanominerals of <4,500 Fe atoms. Global ferritin structure is very stable, resisting 6 M urea and heat (85°C) at neutral pH. Eight pores, each formed by six helices from 3 of the 24 polypeptide subunits, restrict mineral access to reductant, protons, or chelators. Protein-directed transport of Fe and aqueous Fe 3؉ chemistry (solubility Ϸ10 ؊18 M) drive mineralization. Ferritin pores are ''gated'' based on protein crystals and Fe chelation rates of wild-type (WT) and engineered proteins. Pore structure and gate residues, which are highly conserved, thus should be sensitive to environmental changes such as low concentrations of chaotropes. We now demonstrate that urea or guanidine (1-10 mM), far below concentrations for global unfolding, induced multiphasic rate increases in Fe 2؉ -bipyridyl formation similar to conservative substitutions of pore residues. Urea (1 M) or the nonconservative Leu͞Pro substitution that fully unfolded pores without urea both induced monophasic rate increases in Fe 2؉ chelation rates, indicating unrestricted access between mineral and reductant͞chelator. The observation of low-melting ferritin subdomains by CD spectroscopy (melting midpoint 53°C), accounting for 10% of ferritin ␣-helices, is unprecedented. The low-melting ferritin subdomains are pores, based on percentage helix and destabilization by either very dilute urea solutions (1 mM) or Leu͞Pro substitution, which both increased Fe 2؉ chelation. Biological molecules may have evolved to control gating of ferritin pores in response to cell iron need and, if mimicked by designer drugs, could impact chelation therapies in iron-overload diseases.

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supporting

confidence: 70%

mentioning

confidence: 99%

Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral

Liu¹,

Jin²,

Theil³

2003

Proc. Natl. Acad. Sci. U.S.A.

193

245

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“…Dipyridyl is able to remove iron from ferritin, a form in which the iron core is highly protected (16). We have found the iron released to dipyridyl to be an effective catalyst of luminol peroxidation.…”

Section: Discussionmentioning

confidence: 96%

The enhancement of iron‐dependent luminol peroxidation by 2,2′‐Dipyridyl and nitrilotriacetate

Henley

Worwood

1994

J. Biolumin. Chemilumin.

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The generation of radicals from luminol and H2O2, in the presence of iron and iron chelates was monitored by measuring the chemiluminescence produced by further oxidation of these radicals. 2,2'-Dipyridyl enhanced the production of chemiluminescence in the presence of FeSO4, ferritin and haemosiderin but not FeCl3 or horseradish peroxidase. Nitrilotriacetic acid (NTA) enhanced chemiluminescence in the presence of both FeSO4 and FeCl3 but not ferritin or haemosiderin. The enhancement of chemiluminescence by iron chelation may have analytical applications and the process by which these iron chelates are able to generate radicals from the nitrogenous base luminol may be similar to that responsible for their toxic effects on DNA.

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“…Removal of iron from ferritin in solution, by conversion of the mineral to Fe 2+ in solution is slow compared to rates of Fe 2+ oxidation, even when biological reductants such as NADH/FMN are present [83,84]. A role for the protein nanocage in controlling access between the mineral and reductant was discovered in a ferritin with an amino acid substitution for conserved residue leucine 134, where the mineralized protein had greatly increased rates of demineralization, compared to the wild-type protein (100% recovery of mineral was increased 30 times).…”

Section: Ferritin Demineralization and The Nanocage Gated Poresmentioning

confidence: 99%