Ferritin Dynamics in Inflammatory and Cellular Contexts

Ferritin, a ubiquitous iron storage protein, plays a central role in maintaining cellular and systemic iron homeostasis by sequestering excess ferrous iron in a non-toxic ferric form. In inflammatory settings, ferritin synthesis is upregulated as part of the acute‐phase response, thereby limiting free iron that could catalyse harmful reactive oxygen species (ROS) formation. Conversely, controlled ferritin degradation via ferritinophagy releases iron to support essential metabolic processes. Dysregulation of this balance contributes to ferroptosis, an iron‐dependent form of cell death, and amplifies inflammatory signalling through activation of the inflammasome and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF-κB). At the cellular level, macrophage ferritin subunit composition modulates susceptibility to oxidative stress and shapes immune responses, with emerging evidence for specialised roles of heavy and light chains in infection, tissue repair and chronic inflammation.

Research from Nature Portfolio

Recent studies have explored the prognostic significance of circulating ferritin in sepsis. Analysis of large critical‐care cohorts reveals a non‐linear association between serum ferritin levels and short-term as well as long-term mortality, suggesting ferritin as an independent biomarker for risk stratification in septic patients. Separately, investigation of myeloid‐specific deletion of the heavy ferritin subunit in macrophages demonstrates that H-ferritin is indispensable for iron detoxification and defence against iron-induced oxidative damage. H-ferritin–deficient macrophages exhibit impaired nitric oxide synthesis upon inflammatory challenge and heightened sensitivity to iron toxicity, underlining the vital role of subunit composition in modulating both innate immunity and cellular resilience to iron overload.

Ferritin Dynamics in Inflammatory and Cellular Contexts publication trend

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

Technical terms

Ferritin: A protein complex that safely stores iron in a bioavailable, non‐toxic ferric form within cells and circulation.

Ferritinophagy: The selective autophagic degradation of ferritin to release stored iron under conditions of iron demand.

Ferroptosis: A regulated cell‐death pathway driven by iron‐dependent lipid peroxidation and reactive oxygen species accumulation.

Inflammasome: A multiprotein complex that activates inflammatory caspases, leading to cytokine maturation and pyroptotic cell death.

Reactive oxygen species (ROS): Highly reactive molecules derived from molecular oxygen that can damage proteins, lipids and nucleic acids.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB): A transcription factor central to inflammatory and immune gene expression in response to stress signals.

References

1. The Interplay between Intracellular Iron Homeostasis and Neuroinflammation in Neurodegenerative Diseases. Antioxidants (2023).
2. New Perspectives on Circulating Ferritin: Its Role in Health and Disease. Molecules (2023).
3. Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury. Frontiers in Immunology (2019).
4. The relationship between serum ferritin level and clinical outcomes in sepsis based on a large public database. Scientific Reports (2023).
5. H-Ferritin is essential for macrophages’ capacity to store or detoxify exogenously added iron. Scientific Reports (2020).