Unsaturated long chain fatty acids are preferred ferritin ligands enhancing iron biomineralization.

Ferritin is a ubiquitous nanocage protein, which can accommodate up to thousands of iron atoms inside its cavity. Besides its iron storage function, a new role as fatty acid binder has been proposed for this protein. The interaction of apo horse spleen ferritin (HoSF) with a variety of lipids has been here investigated through NMR ligand-based experiments, to provide new insights into the mechanism of ferritin/lipid interactions and the link with iron mineralization. 1D DOSY and STD NMR experiments established a stronger interaction of ferritin with unsaturated fatty acids with respect to saturated fatty acids, detergents and bile acids. Mineralization assays showed that oleate caused the most efficient increase in the initial rate of iron oxidation and the highest formation of ferric species in HoSF. The comprehension of the factors inducing a faster biomineralization is an issue of the utmost importance, given the assessed association of ferritin levels with metabolic syndromes, such as insulin resistance and diabetes, characterized by fatty acid concentration dysregulation. The human ferritin H chain homopolymer (HuHF), endowed with ferroxidase activity, was also tested for its fatty acid binding capabilities. Assays show that oleate can bind with high affinity to HuHF, without altering the reaction rates at the ferroxidase site.