The ferritins: molecular properties, iron storage function and cellular regulation

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Ferritin is a ubiquitous iron storage protein essential for iron metabolism, detoxification, and reserve.
• Its conserved three-dimensional structure, a hollow shell of 24 subunits, can store up to 4500 Fe(III) atoms.
• Vertebrate ferritins comprise H- and L-subunits, while plant and bacterial ferritins contain H-type chains with iron-oxidizing centers.

Purpose of the Study:

• To review the functional mechanisms and regulation of ferritin.
• To explore the structural conservation and variations in ferritin across different species.
• To elucidate the roles of H- and L-chains in iron storage and mobilization.

Main Methods:

• Structural analysis of ferritins from humans, horses, bullfrogs, and bacteria.
• Investigation of subunit composition (H and L chains) and their associated functions.
• Examination of translational regulation mechanisms, including the iron regulatory protein (IRP) and iron-regulatory element (IRE) interactions.

Main Results:

• Ferritin exhibits a highly conserved 4-helix bundle subunit structure, despite significant variations in amino acid sequences.
• H-chains are crucial for catalyzing Fe(II) oxidation, while L-chains facilitate iron core formation.
• Mammalian ferritin synthesis is translationally regulated by iron levels via the IRP/IRE system, linking iron and citrate metabolism.

Conclusions:

• Ferritin's conserved structure and dual H/L subunit composition enable efficient iron storage and detoxification.
• The IRP/IRE system provides tight control over cellular iron uptake and ferritin synthesis.
• Understanding ferritin's complex interrelationships with other intracellular iron complexes remains a significant challenge.