Ferritin for the clinician

Abstract

Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage.

Figure 1

Ferritin Structure: Apoferritin forms a roughly spherical container within which ferric iron is stored as a ferrihydrite mineral. Apoferritin refers to the iron-free form of the protein; the iron-containing form is termed holoferritin or simply ferritin. The apoferritin shell is composed of 24 subunits of two types, termed H and L, the ratio of which varies widely depending on tissue type and inflammation. Iron is toxic in cellular systems because of its capacity to generate reactive species (shown as yellow spheres) which can directly damage DNA and proteins.

Figure 2

Intracellular Iron Homeostasis: Ferritin functions as a ferroxidase, converting Fe²⁺ to Fe³⁺ as iron is internalized and sequestered in the ferritin mineral core. Reactive species (shown as yellow spheres) can directly damage DNA and proteins. DMT1 = divalent metal ion transporter 1, Tf = Transferrin, TfR = Transferrin receptor.

Figure 3

Decline of ferritin with therapeutic phlebotomy in a patient with hereditary hemochromatosis.