What protein functions to store or transport iron? Understanding Ferritin and Transferrin

December 28, 2025 •

3 min read

Iron is a vital mineral, but free iron is toxic to cells because it can generate damaging free radicals. The human body has developed a sophisticated system involving specific proteins, primarily ferritin and transferrin, to safely manage the storage and transport of this essential element.

Quick Summary

Ferritin stores iron within cells, while transferrin transports iron through the bloodstream to tissues. These proteins are crucial for regulating iron levels to prevent both deficiency and toxicity.

Key Points

Transferrin is the transport protein: This glycoprotein carries iron through the bloodstream to various tissues, such as the bone marrow, where it is needed.
Ferritin is the storage protein: Located primarily within the cells of the liver, spleen, and bone marrow, this protein stores iron in a non-toxic form.
Iron is absorbed via transferrin receptors: Iron-bound transferrin binds to receptors on cell surfaces, initiating endocytosis to deliver iron internally.
Ferritin stores iron as ferrihydrite: Inside the ferritin shell, iron is oxidized to its ferric state and stored as a crystalline mineral core, which prevents its toxic free-radical activity.
Hemosiderin stores excess iron: When ferritin storage capacity is exceeded, excess iron forms an insoluble aggregate called hemosiderin, which is less accessible for use.
Iron levels are regulated by hepcidin: The hormone hepcidin controls the amount of iron released into the bloodstream by regulating the iron exporter protein, ferroportin.

The Vital Role of Iron in the Human Body

Iron is one of the most essential trace elements, playing a critical role in numerous biological processes, including oxygen transport, DNA synthesis, and cellular respiration. While most iron in vertebrates is bound to hemoglobin in red blood cells, unbound iron is toxic. The body relies on ferritin and transferrin to manage this balance.

The Primary Iron Transport Protein: Transferrin

Transferrin is a glycoprotein in blood plasma that transports iron. Synthesized mainly by the liver, it binds tightly to ferric iron ($Fe^{3+}$), keeping it soluble and non-reactive in the bloodstream. Each transferrin molecule can carry two ferric iron atoms.

How Transferrin Works

Absorption and Release: Iron from the diet or recycled from red blood cells is oxidized to $Fe^{3+}$ and binds to transferrin in the plasma.
Targeting Cells: Transferrin delivers iron to cells via receptor-mediated endocytosis, particularly to cells with high iron needs like those in bone marrow.
Endocytosis and Iron Release: The transferrin-receptor complex is internalized. Within an acidic endosome, iron is released from transferrin.
Recycling: The empty transferrin-receptor complex is returned to the cell surface, releasing apotransferrin back into the blood.

The Key Iron Storage Protein: Ferritin

Ferritin is the main protein for storing iron inside cells, acting as a buffer against iron imbalance. It is abundant in the liver, spleen, and bone marrow. Ferritin forms a hollow structure capable of storing up to 4,500 iron atoms as a mineral core.

How Ferritin Stores Iron

Entry and Oxidation: Iron enters ferritin in the ferrous ($Fe^{2+}$) state and is oxidized to the ferric ($Fe^{3+}$) state by the protein's H-subunits.
Core Formation: The ferric iron is stored as ferrihydrite within the protein core, keeping it safe and non-toxic.
Iron Release: Stored iron is released when needed through a process called ferritinophagy, involving lysosomal degradation of ferritin.

The Role of Hemosiderin in Iron Overload

If ferritin storage capacity is overwhelmed, excess iron is stored as hemosiderin, an insoluble aggregate of denatured ferritin found primarily in macrophages. Hemosiderin iron is less available and its accumulation is associated with iron overload disorders.

Regulation of Iron Metabolism

Systemic iron balance is regulated by hepcidin, a hormone produced in the liver. Hepcidin controls the iron exporter ferroportin. High iron levels increase hepcidin, leading to ferroportin degradation and reduced iron release into the blood. Low iron suppresses hepcidin, increasing iron release.

A Comparison: Transferrin vs. Ferritin


Feature	Transferrin	Ferritin	Hemosiderin
Function	Transports iron in blood	Stores iron intracellularly	Stores excess iron as aggregate
Location	Circulating in blood	In cells (liver, spleen, marrow)	In cells (macrophages)
Iron Capacity	2 $Fe^{3+}$ per molecule	Up to ~4500 atoms per molecule	High capacity, aggregated
Form of Iron	Ferric iron ($Fe^{3+}$)	Ferric iron ($Fe^{3+}$) as ferrihydrite	Insoluble ferric iron aggregate
Toxicity	Prevents toxicity in blood	Prevents toxicity inside cells	Indicates high iron burden
Release Mechanism	Releases to receptors in endosomes	Released via ferritinophagy	Slowly degraded

Conclusion

Transferrin transports iron through the body, while ferritin stores it within cells, and hemosiderin stores excess iron. This system, regulated by hepcidin, prevents iron toxicity while ensuring its availability for vital processes. Understanding these proteins is crucial for managing iron-related health conditions.

For more detailed information, see: {Link: IntechOpen https://www.intechopen.com/chapters/79004}.

Frequently Asked Questions

Ferritin is primarily an intracellular storage protein for iron, keeping it safely sequestered within cells. Transferrin is a transport protein that circulates in the blood, carrying iron to different parts of the body that need it.

Transferrin saturation is a measure that indicates the percentage of transferrin protein that is currently bound to iron. Low saturation can signal iron deficiency, while high saturation may indicate iron overload.

If there is an excess of iron, ferritin levels will increase as the protein stores more iron. However, if ferritin's capacity is exceeded, iron will aggregate into hemosiderin. This can lead to iron overload, which can damage organs over time.

Iron is released from ferritin through a controlled, selective autophagic process called ferritinophagy. The cargo receptor NCOA4 binds to ferritin, targeting it for degradation in lysosomes and releasing the stored iron.

Yes, small amounts of ferritin are secreted from cells and circulate in the serum. Measuring serum ferritin levels is a standard laboratory test to estimate the body's total iron stores.

Hepcidin is a hormone that regulates systemic iron balance. When iron levels are high, hepcidin rises and causes the degradation of ferroportin, an iron exporter. This limits the release of iron into the blood.

Free iron is dangerous because it can catalyze reactions that produce highly damaging reactive oxygen species, like free radicals. These can cause damage to lipids, proteins, and DNA, which is why iron is always transported and stored in a bound, non-toxic form.