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Pharmaceuticals 2018, 11(4), 120; https://doi.org/10.3390/ph11040120

Reductive Mobilization of Iron from Intact Ferritin: Mechanisms and Physiological Implication

1
Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA
2
Department of Chemistry & Biomolecular Science, Clarkson University, Potsdam, NY 13699, USA
*
Authors to whom correspondence should be addressed.
Received: 14 October 2018 / Revised: 31 October 2018 / Accepted: 1 November 2018 / Published: 5 November 2018
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
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Abstract

Ferritins are highly conserved supramolecular protein nanostructures composed of two different subunit types, H (heavy) and L (light). The two subunits co-assemble into a 24-subunit heteropolymer, with tissue specific distributions, to form shell-like protein structures within which thousands of iron atoms are stored as a soluble inorganic ferric iron core. In-vitro (or in cell free systems), the mechanisms of iron(II) oxidation and formation of the mineral core have been extensively investigated, although it is still unclear how iron is loaded into the protein in-vivo. In contrast, there is a wide spread belief that the major pathway of iron mobilization from ferritin involves a lysosomal proteolytic degradation of ferritin, and the dissolution of the iron mineral core. However, it is still unclear whether other auxiliary iron mobilization mechanisms, involving physiological reducing agents and/or cellular reductases, contribute to the release of iron from ferritin. In vitro iron mobilization from ferritin can be achieved using different reducing agents, capable of easily reducing the ferritin iron core, to produce soluble ferrous ions that are subsequently chelated by strong iron(II)-chelating agents. Here, we review our current understanding of iron mobilization from ferritin by various reducing agents, and report on recent results from our laboratory, in support of a mechanism that involves a one-electron transfer through the protein shell to the iron mineral core. The physiological significance of the iron reductive mobilization from ferritin by the non-enzymatic FMN/NAD(P)H system is also discussed. View Full-Text
Keywords: ferritin; iron mobilization; chaotropes; flavin nucleotide; electron transfer; kinetics ferritin; iron mobilization; chaotropes; flavin nucleotide; electron transfer; kinetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Bou-Abdallah, F.; Paliakkara, J.J.; Melman, G.; Melman, A. Reductive Mobilization of Iron from Intact Ferritin: Mechanisms and Physiological Implication. Pharmaceuticals 2018, 11, 120.

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