Structural biology of ferritin nanocages

Ferritin is a ubiquitous and evolutionarily conserved iron-storage protein that plays a fundamental role in cellular iron homeostasis. By catalyzing the oxidation of ferrous iron and sequestering it as a ferric mineral within a protein nanocage, ferritin prevents toxic accumulation of labile iron and reactive oxygen species that damage proteins, lipids, and DNA. In humans, ferritin assembles into a 24-subunit nearly spherical shell enclosing a central cavity that safely stores thousands of iron atoms. This organized architecture enables ferritin to act as both an efficient iron detoxification system and a dynamic intracellular iron reservoir. Recent advances in cryo-electron microscopy (cryo-EM) have transformed ferritin research by revealing its structural organization, molecular interactions, and functional states at high resolution. Additionally, beyond protein-protein interactions, cryo-EM now enables direct visualization of ferritin-mediated biomineralization, allowing in situ observation of iron nucleation, mineral growth, and core organization within intact nanocages. Together, these advances establish cryo-EM as a transformative tool for elucidating ferritin structure, dynamics, and function - reshaping our understanding of iron metabolism and guiding the rational design of ferritin-based nanomaterials for biomedical applications.