The importance of eukaryotic ferritins in iron handling and cytoprotection

Ferritins, the main intracellular iron storage proteins, have been studied for over 60years, mainly focusing on the mammalian ones.Thisallowedtheelucidationofthestructureoftheseproteins and the mechanisms regulating their iron incorporation and mineralization.However,ferritinispresentinmost,althoughnot all, eukaryotic cells, comprising monocellular and multicellular invertebratesandvertebrates.Theaimofthisreviewistoprovide anupdateonthegeneralpropertiesofferritinsthatarecommonto variouseukaryoticphyla(exceptplants),andtogiveanoverview on the structure, function and regulation of ferritins. An update on the animal models that were used to characterize H, L and mitochondrialferritinsisalsoprovided.Thedatashowthatferritin structure is highly conserved among different phyla. It exerts an important cytoprotective function against oxidative damage and playsaroleininnateimmunity,whereitalsocontributestoprevent 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 ferritin in mammals.