Iron detoxification and storage in human cytosolic ferritins

Bugg, Zinnia Daisy Poppy Clover Primrose (2025) Iron detoxification and storage in human cytosolic ferritins. Doctoral thesis, University of East Anglia.

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Abstract

Iron is essential for almost all life, by playing a key role in a range of processes, including respiration and DNA synthesis. Iron also presents organisms with two problems: ferric iron is highly insoluble and so has poor bioavailability and ferrous iron can readily produce reactive oxygen species, meaning that it is potentially toxic. Ferritins are a family of iron storage proteins that evolved to overcome these problems by both detoxifying and storing iron in a safe but bioavailable form. Ferritins are 24-mers and mammalian cytosolic ferritins are made up of two subunit types, H- and L-chains, which co-assemble into heteropolymer protein cages surrounding an internal cavity. The two subunit types fulfil distinct mechanistic roles, with H-chain promoting controlled oxidation and hence detoxification of ferrous iron, and L-chain promoting the synthesis of a ferric oxo mineral that can be safely stored within the ferritin central cavity. The heteropolymeric nature of physiological ferritins has presented challenges for ferritin research in terms of understanding how the two subunit types function together by a consequence of the advent of recombinant DNA technology that enabled researchers to readily obtain H- and L-chain ferritins as recombinantly overexpressed homopolymers. Thus, while much has been learned about the properties of the individual subunits, there has been little attention paid to the mechanisms of iron detoxification and storage in physiological heteropolymers. Here, the mechanisms of iron oxidation and mineralisation of human H- and L-chain cytosolic ferritins are explored for both homopolymers and heteropolymers. To synthesise heteropolymers in vitro, methods from published literature were explored and found to be unsuitable, and so a novel method for heteropolymer cage formation was developed and optimised. This controllable production of ferritin heteropolymers provides a rare opportunity to gain insight into the mechanisms of naturally occurring ferritins, which is explored in this report.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Depositing User:	Chris White
Date Deposited:	04 Nov 2025 09:33
Last Modified:	04 Nov 2025 09:33
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100882
DOI:

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