Ferritins, the main intracellular iron storage proteins, have been studied for over 60 years, mainly focusing on the mammalian ones. This allowed the elucidation of the structure of these proteins and the mechanisms regulating their iron incorporation and mineralization. However, ferritin is present in most, although not all, eukaryotic cells, comprising monocellular and multicellular invertebrates and vertebrates. The aim of this review is to provide an update on the general properties of ferritins that are common to various eukaryotic phyla (except plants), and to give an overview on the structure, function and regulation of ferritins. An update on the animal models that were used to characterize H, L and mitochondrial ferritins is also provided. The data show that ferritin structure is highly conserved among different phyla. It exerts an important cytoprotective function against oxidative damage and plays a role in innate immunity, where it also contributes to prevent parenchymal tissue from the cytotoxicity of pro-inflammatory agonists released by the activation of the immune response activation. Less clear are the properties of the secretory ferritins expressed by insects and molluscs, which may be important for understanding the role played by serum ferritin in mammals.

Biogenic magnetite is a fascinating example of how nature can generate functional magnetic nanostructures. Inspired by the magnetic bacteria, an attempt is made to mimic their magnetic properties, rather than their structures, to create living magnets at room temperature. The non‐magnetic probiotic bacteria Lactobacillus fermentum and Bifidobacteria breve are used as bioplatforms to densely arrange superparamagnetic nanoparticles on their external surfaces, thus obtaining the artificial magnetic bacteria. Magnetic probiotic bacteria can be produced by using superparamagnetic maghemite nanoparticles assembled at their surfaces. They present a collective ferromagnetic phase at room temperature. The blocking temperature of these maghemite nanoparticles increases more than 100 K when assembled at the artificial magnetic bacteria.

Living organisms have developed a chemical machinery based on the ferritin protein for the storage, under a nontoxic form, of the iron that is not required for immediate metabolic purposes. Whereas free iron causes extensive cell damage, ferritin iron is not toxic, yet still available for cell requirements. However, iron storage in ferritin is increasingly being recognized as a crucial process related with some neurodegenerative disorders and therefore, an understanding of the management of iron in the brain, especially the processes of iron uptake and release in ferritin, is compulsory to clarify the role of this metalloprotein in these neuropathologies.Although knowledge of iron storage and iron release in ferritin is nowadays still limited, even less information is currently available about the influence of free metal ions and other brain metalloproteins in these processes.In this sense, this review is an excellent opportunity to collect all the information today available about the influence of metals and metalloproteins in ferritin loading and unloading events, which until now are dispersed in the literature.Furthermore, we will focus on the importance of all the above-mentioned interactions in the brain, since the importance of the correct and safe balance of metals in the brain after their well-known implication in neurodegenerative 52 processes such as the lzheimer's ( ), Parkinson (P ) and prion protein (PP ) diseases is obvious. In this work, we will not only recall the importance and role of ferritin in the brain but also the putative influence of the interaction between ferritin and some metals and/or metalloproteins and other biomolecules on these neurological dysfunctions. The final part of the review will be devoted to draw some guidelines to where the future prospects point to on the basis of the existing information.

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Background: The high stability and strong self-assembly properties made ferritins the most used proteins for nanotechnological applications. Human ferritins are made of 24 subunits of the H-and Ltype that coassemble in an almost spherical nanocage 12 nm across, delimiting a large cavity. The mechanism and kinetics of ferritin self-assembly and why H/L heteropolymers formation is favored over the homopolymers remain unclarified. Methods: We used the Fluorescence Resonance Energy Transfer (FRET) by binding multiple donor or acceptor Alexa Fluor fluorophores on the outer surface of human H and L ferritins and then denaturing and reassembling them in different proportions and conditions. Results: The FRET-efficiency increase from <0.3 of the disassembled to >0.7 in the reassembled allowed to study the self-assembly kinetics. We found that their assembly was complete in about one hour, and that the initial rate of self-assembly of H/L heteropolymers was slightly faster than that of the H/H homopolymers. Then, by adding various proportions of unlabeled H or L-chains to the FRET system we found that the presence of the L-chains displaced the formation of H-H dimers more efficiently than that of the H-chains. Conclusion: Heterodimeric (H/L) subunit association is preferred during H/L heteropolymers formation. The H-chains arrange at distant positions on the heteropolymeric shell until they reach a number above eight, when they start to co-localize and the ferroxidase activity of the heteropolymer reaches a plateau. General significance: This favored formation of H/L heterodimers, which is the initial step in ferritin self-assembly, contributes to explain the preferred formation of H/L heteropolymers over the H or L homopolymers. Keywords