Iron Metabolism and Ferritin Dynamics

Iron is an essential micronutrient that underpins oxygen transport, DNA synthesis and cellular respiration. Dietary iron is absorbed primarily in the duodenum, where enterocytes export ferrous iron via ferroportin into the circulation. In plasma, iron is bound by transferrin and delivered to tissues through receptor-mediated endocytosis. Cellular iron homeostasis is governed by iron regulatory proteins that sense cytosolic iron and modulate expression of iron-handling genes. Excess iron is sequestered in ferritin, a hollow protein nanocage that stores up to 4,500 iron atoms in a bioavailable yet non-toxic form. Ferritin dynamics involve coordinated synthesis of apoferritin, iron incorporation, and ferritinophagy—a selective autophagic process that releases iron under demand. Dysregulation of these pathways contributes to anaemia of chronic disease, iron overload disorders and ferroptotic cell death. Recent structural biology has revealed diverse ferritin assemblies across species, illuminating channels that guide iron entry and exit. In parallel, advances in molecular imaging and single-cell analysis have mapped iron fluxes in immune cells, uncovering how macrophage ferritin turnover modulates systemic iron recycling. Together, these insights refine our understanding of iron trafficking and ferritin kinetics, with implications for therapeutic modulation in infection, neurodegeneration and metabolic disease.

Research from Nature Portfolio

Recent studies have elucidated the structural basis of ferritin assembly using high-resolution cryo-EM, identifying distinct gating mechanisms that regulate iron mineralisation and release. Investigations into ferritinophagy have uncovered a receptor-mediated pathway in which a nuclear coactivator functions as a selective autophagy cargo adaptor, linking ferritin to autophagosomes and controlling intracellular iron availability. In addition, time-lapse imaging of macrophages has demonstrated that dynamic ferritin turnover shapes the inflammatory response, with rapid ferritin degradation enhancing iron export and limiting pathogen proliferation.

Iron Metabolism and Ferritin Dynamics publication trend

The graph below shows the total number of articles in iron metabolism and ferritin dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Ferritin: A spherical protein complex that stores iron in a soluble, non-toxic form and releases it in a controlled manner.

Apoferritin: The iron-free protein shell of ferritin, which assembles into a hollow cage awaiting iron mineralisation.

Ferroportin: The sole known cellular iron exporter located on the basolateral membrane of enterocytes and macrophages.

Hepcidin: A liver-derived peptide hormone that binds ferroportin and induces its internalisation, thereby reducing iron export.

Iron regulatory proteins (IRPs): Cytosolic sensors that bind iron-responsive elements in mRNA to control translation of iron-related genes.

Ferritinophagy: A selective autophagic process that degrades ferritin to liberate stored iron when cytosolic demand increases.

References

1. Regulation of Synthesis and Turnover of Ferritin in Rat Liver. Journal of Biological Chemistry (1966).
2. FERRITIN II. APOFERRITIN OF HORSE SPLEEN. Journal of Biological Chemistry (1943).
3. Factors Affecting the Synthesis of Transferrin by Rat Tissue Slices. Journal of Biological Chemistry (1969).