Fe3ferritin

Fe3ferritin is a descriptive term rather than a distinct protein class. It refers to ferritin complexes in which the stored iron is predominantly in the ferric oxidation state (Fe3+) and organized into a mineral-like core inside the protein shell. Ferritin is a ubiquitous iron storage protein that forms a roughly spherical 24-subunit nanocage. The external diameter is about 12 nanometers, and the internal cavity is roughly 8 nanometers across, enabling storage of thousands of iron atoms as Fe3+ in a ferrihydrite-like mineral.

Iron uptake and core formation occur when Fe2+ enters ferritin through channels and is oxidized to Fe3+ at the ferroxidase center, primarily in H-subunits. The oxidized iron then precipitates as ferrihydrite-like ferric oxide within the core. The L-subunits support stability and long-term storage of the mineral. Iron release happens by reduction of Fe3+ back to Fe2+, allowing iron to exit the shell for cellular use when needed.

Biological role and distribution: Ferritin buffers cellular iron, protecting against iron-induced oxidative stress and helping maintain iron homeostasis. In humans, ferritin is found in the cytosol and mitochondria of many cell types, and serum ferritin is commonly used as a biomarker of total body iron stores and inflammation. The H/L-subunit ratio within ferritin varies by tissue and influences ferroxidase activity and storage capacity.

Clinical and research relevance: Dysregulation of ferritin levels is associated with iron deficiency, anemia of chronic disease, and iron overload disorders. Ferritin nanocages are explored as platforms for drug delivery and imaging. The term Fe3ferritin highlights the ferric iron state within the ferritin core, but ferritin generally stores iron in a ferric, mineralized form across species.