Iron Metabolism and Absorption Mechanisms

Iron is an essential micronutrient that underpins myriad biological processes, including oxygen transport, DNA synthesis and cellular respiration. Its redox reactivity underlies both its physiological utility and potential toxicity, necessitating tight regulation at systemic and cellular levels. Dietary iron is absorbed predominantly in the duodenum as heme and non-heme forms. Heme iron is liberated from haemoglobin and myoglobin by proteolysis and translocated intact across the apical membrane, whereas non-heme iron is first reduced from ferric (Fe3+) to ferrous (Fe2+) state by a duodenal reductase before uptake via a divalent metal transporter. Once inside enterocytes, iron may be stored in ferritin or exported across the basolateral membrane by ferroportin, the only known cellular iron exporter. The liver-derived peptide hepcidin modulates ferroportin abundance in response to systemic iron needs, inflammation and erythropoietic demand. In circulation, iron binds to transferrin for delivery to peripheral tissues, where cells internalise transferrin–iron complexes via receptor-mediated endocytosis. Intracellular iron is utilised for haem and Fe–S cluster biosynthesis or re-sequestered within ferritin. Macrophages reclaim iron from senescent erythrocytes and recirculate it through the same export machinery. Dysregulation of these pathways underlies iron-deficiency anaemia, hereditary haemochromatosis and anaemia of chronic disease, with global prevalence and significant public-health implications.

Research from Nature Portfolio

A study investigating acute disruption of the hepatic endo-lysosomal system in vivo revealed that rapid loss of endosomal compartments triggers a cascade of compensatory responses in iron homeostasis. Within days of endosome depletion, hepatic iron stores declined sharply, coinciding with elevated levels of ferroportin at the cell surface. Concurrently, expression of transferrin receptor 1 increased while hepatic production of the iron-regulatory hormone declined, leading to higher serum iron and binding capacity. These findings underscore the dynamic role of endosomal trafficking in coordinating hepatic iron retention and systemic distribution, and highlight the speed at which liver iron pools can respond to intracellular sorting defects.

Iron Metabolism and Absorption Mechanisms publication trend

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

Technical terms

Hepcidin: Peptide hormone produced by the liver that negatively regulates iron export by binding to ferroportin.

Ferroportin: Transmembrane iron exporter located on enterocytes, macrophages and hepatocytes, controlled by hepcidin.

Transferrin: Plasma glycoprotein that binds ferric iron and delivers it to cells via receptor-mediated uptake.

Divalent metal transporter (DMT1): Apical membrane protein in enterocytes responsible for ferrous iron uptake from the intestinal lumen.

Endocytosis: Cellular process by which extracellular molecules are internalised within membrane-bound vesicles.

References

1. Iron metabolism and laboratory testing for iron status. Medicinski podmladak (2016).
2. Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis. Scientific Reports (2017).
3. Hepatocytes and reticulocytes have different mechanisms for the uptake of iron from transferrin.. Journal of Biological Chemistry (1988).