Multiple pathways for mineral core formation in mammalian apoferritin. The role of hydrogen peroxide

Guanghua Zhao, Fadi Bou-Abdallah, Paolo Arosio, Sonia Levi, Christine Janus-Chandler, N. Dennis Chasteen

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Abstract

Human ferritins sequester and store iron as a stable FeOOH(s) mineral core within a protein shell assembled from 24 subunits of two types, H and L. Core mineralization in recombinant H- and L-subunit homopolymer and heteropolymer ferritins and several site-directed H-subunit variants was investigated to determine the iron oxidation/hydrolysis chemistry as a function of iron flux into the protein. Stopped-flow absorption spectrometry, UV spectrometry, and electrode oximetry revealed that the mineral core forms by at least three pathways, not two as previously thought. They correspond to the ferroxidase, mineral surface, and the Fe(II) + H2O2 detoxification reactions, respectively: 2Fe2++O2+4H2O→ 2FeOOH(core)+H2O2+4H+ (1) 4Fe2+ + O2 + 6H2O → 4FeOOH(core) + 8H+ (2) 2Fe2+ + H2O2 + 2H2O → 2FeOOH(core) + 4H+ (3) The H-subunit catalyzed ferroxidase reaction 1 occurs at all levels of iron loading of the protein but decreases with increasing iron added (48-800 Fe(II)/protein). Reaction 2 is the dominant reaction at 800 Fe(II)/protein, whereas reaction 3 occurs largely at intermediate iron loadings of 100-500 Fe(II)/protein. Some of the H2O2 produced in reaction 1 is consumed in the detoxification reaction 3; the 2/1 Fe(II)/H2O2 stoichiometry of reaction 3 minimizes hydroxyl radical production during mineralization. Human L-chain ferritin and H-chain variants lacking functional nucleation and/or ferroxidase sites deposit their iron largely through the mineral surface reaction 2. H2O2 is shown to be an intermediate product of dioxygen reduction in L-chain as well as in H-chain and H-chain variant ferritins.

Original languageEnglish
Pages (from-to)3142-3150
Number of pages9
JournalBiochemistry
Volume42
Issue number10
DOIs
Publication statusPublished - Mar 18 2003

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Zhao, G., Bou-Abdallah, F., Arosio, P., Levi, S., Janus-Chandler, C., & Chasteen, N. D. (2003). Multiple pathways for mineral core formation in mammalian apoferritin. The role of hydrogen peroxide. Biochemistry, 42(10), 3142-3150. https://doi.org/10.1021/bi027357v