Iron Oxidation and Core Formation in Recombinant Heteropolymeric Human Ferritins

Area of Science:

• Biochemistry
• Protein Structure and Function
• Iron Metabolism

Background:

• Ferritin is an iron storage protein composed of H (heavy) and L (light) subunits.
• H-subunits contain a ferroxidase center (FC) essential for iron oxidation.
• L-subunits' role in iron oxidation and core formation is not fully understood.

Purpose of the Study:

• To investigate the role of the L-subunit in human ferritin's iron oxidation and core formation.
• To compare the function of H-rich and L-rich heteropolymeric ferritins with homopolymeric H-subunit ferritin.

Main Methods:

• Utilized human recombinant heteropolymeric ferritins (H-rich and L-rich) and homopolymeric H-subunit ferritin (HuHF).
• Analyzed iron oxidation stoichiometry, H2O2 generation, and intermediate formation at the ferroxidase center.
• Assessed iron core size and ferroxidase activity regeneration rates.

Main Results:

• H-rich ferritin exhibited efficient iron oxidation with 2:1 Fe(II):O2 stoichiometry and H2O2 generation, similar to HuHF.
• H-rich ferritin showed faster ferroxidase activity regeneration and formed larger iron cores compared to HuHF.
• L-rich ferritin facilitated iron oxidation at the FC and also at the mineral surface.

Conclusions:

• The L-subunit plays a crucial role in facilitating iron turnover at the ferroxidase center.
• The L-subunit also contributes to the mineralization of larger iron cores within the ferritin shell.
• Ferritin subunit composition significantly influences iron oxidation and mineralization processes.