Iron Stories

Ferritins, the senior proteins of iron metabolism

Paolo Arosio
Università degli Studi di Brescia
Department of Molecular and Translational Medicine
Brescia, Italy.

Why ferritins?

• Ferritin is the first discovered molecule implicated in iron metabolism (1937), about a decade before transferrin.
• It is among the most ancient molecules of life, expressed in all phila, from archea, eubacteria, plants, animals to humans.
• It is the protein richest in iron, as it can contain up to thousands of iron atoms in a safe form.
• It is everywhere in the cell (cytosol, nucleus, mitochondria, plastids) and also in the extracellular space and body fluids, with various functions.
• Its levels are tightly regulated by iron in animals and plants (and perhaps also in bacteria), serving as an indicator of cell and systemic iron status in most organisms
• It is beautifully built by well-designed 4-helical-bundle subunits the make a shell – nanobox or nanocage – and it is so strong that it can withstand harsh conditions and large modifications of amino acid sequences
• It has a flexible quaternary structure formed by one or more different subunit types that form a 24-mer shell, resulting in hundreds or thousands of different possible isoferritins
• It is one thing with its iron, which is released and recycled only after protein disruption. Thi is done by a complex and regulated mechanism (ferritinophagy) that takes the protein to the lysosomes for its digestion .
• Ferritin and transferrin set the foundation of the Bioiron Society, promoted by Pauline Harrison (the ferritin Lady) and Phil Eisen (the transferrin Lord)
• Last but not least, ferritin and me (PA) have been together for more than 40 years.

What are Ferritins Good For?

• What ferritins do?Ferritins are good, if not very good.Antioxidant: their ferroxidase activity positively competes with Fenton reaction for Fe(II) and h4O2, thus limiting the production of toxic free radicals in all organisms. Protection from death: they protect cells from apoptosis and probably also from ferroptosis. Protection from infections: they protect mice from malaria, fishes and shell-fishes from various infections. Organ protection: they protect from cardiac complications, from from acute kidney diseases, from atherosclerosis and also cells from calcification. Other positive functions on photosynthesis, cell proliferation and other mechanisms have been described.
• Ferritins are bad only rarely.Few reports claimed that some ferritin types may promote apoptosis. Ferritin was found necessary for the progression of glioblastoma stem-like cells. When mutated the non-ferroxidase L-ferritin may cause neurodegeneration.
• Ferritins are even useful. Because it their easy to produce, purify, store, and also because of it unique self-assembly and high stability properties, ferritins are the most used protein in bio-nanotechnology. They are versatile biotech tools for encapsulating various molecules and ionic species, for synthesizing mineral cores, semiconductor particles and metal alloys and for carrying various epitopes/antigens. Ferritins have been used in the production of semiconductors and nanoelectronics, in drug delivery systems, in nanoparticles for biomedical diagnosis and more is to come.

In Summary:

The Ferritins have a remarkable history, are still much alive in present time and promise a bright future to those interested in them.

Download Article: Ferritins, the Senior Proteins of Iron Metabolism by P. Arosio

posted: March 17, 2018