Iron Homeostasis and Oxidative Stress Modulation

Iron is indispensable for processes ranging from oxygen transport to DNA synthesis, yet its redox activity makes unbound iron a potent catalyst of reactive oxygen species (ROS). Living organisms have evolved intricate systems to maintain iron homeostasis, balancing absorption, storage and recycling to prevent deficiency or toxicity. At the systemic level, dietary iron is taken up by intestinal enterocytes via divalent metal transporter 1 and exported through ferroportin under the regulation of the hormone hepcidin. Intracellularly, iron regulatory proteins sense labile iron pools and adjust the expression of proteins such as ferritin, which safely sequesters excess iron. Disruption of these pathways can tip the balance towards oxidative stress, driving lipid peroxidation, protein oxidation and nucleic acid damage. Conversely, antioxidant defences—enzymatic and small-molecule—scavenge ROS and modulate iron-catalysed radical formation. The interplay between iron handling and redox homeostasis underpins conditions as diverse as anaemia, neurodegeneration, cardiovascular disease and infection, and informs strategies from food fortification to chelation therapy.

Research from Nature Portfolio

Recent studies have elucidated how intrinsic and extrinsic factors govern iron-polyphenol interactions that lead to discolouration and impaired bioavailability in fortified foods. Using a systematic experimental design, temperature, pH and iron salt identity were identified as primary determinants of iron–catechol complexation, while two-way interactions between pH and salt type or concentration further modulate complex stoichiometry. Advanced spectroscopic analyses linked specific absorbance shifts to complex composition, and mass spectrometry confirmed the architectures of the iron–catechol adducts. These insights offer a framework for optimising food formulations to minimise oxidative discolouration and enhance iron uptake.

Iron Homeostasis and Oxidative Stress Modulation publication trend

The graph below shows the total number of articles in iron homeostasis and oxidative stress modulation across all publications each year (not limited to Nature Index journals).

Technical terms

Fenton reaction: A chemical reaction in which ferrous iron catalyses the conversion of hydrogen peroxide into highly reactive hydroxyl radicals.

Hepcidin: A peptide hormone produced by the liver that inhibits intestinal iron export by inducing degradation of ferroportin.

Ferroportin: The sole known cellular iron exporter, present on enterocytes, macrophages and hepatocytes.

Ferritin: A nanocage protein complex that stores iron in a non-reactive ferric form and releases it when required.

Reactive oxygen species (ROS): Unstable oxygen-containing molecules, such as superoxide and hydrogen peroxide, capable of damaging biomolecules.

References

1. Food‐borne polyphenols: A biocompatible anchor recuperating iron homeostasis. Food Frontiers (2023).
2. Inhibition of Metal-Polyphenol Complex in Tea Fortified with Encapsulated Iron. Food and Bioprocess Technology (2024).
3. Quercetin Inhibits Hephaestin Expression and Iron Transport in Intestinal Cells: Possible Role of PI3K Pathway. Nutrients (2023).
4. Revealing the main factors and two-way interactions contributing to food discolouration caused by iron-catechol complexation. Scientific Reports (2020).