Metal cofactors trafficking and assembly in the cell: A molecular view

Metal ions are essential cofactors required by the proteome of organisms from any kingdom of life to correctly exert their functions. Dedicated cellular import, transport and homeostasis systems assure that the needed metal ion is correctly delivered and inserted into the target proteins and avoid the presence of free metal ions in the cell, preventing oxidative damaging. Among metal ions, in eukaryotic organisms copper and iron are required by proteins involved in absolutely essential functions, such as respiration, oxidative stress protection, catalysis, gene expression regulation. Copper and iron binding proteins are localized in essentially all cellular compartments. Copper is physiologically present mainly as individual metal ion. Iron can be present both as individual metal ion or as part of cofactors, such as hemes and iron-sulfur (Fe-S) clusters. Both metal ions are characterized by the ability to cycle between different oxidation states, which enable them to catalyze redox reactions and to participate in electron transfer processes. Here we describe in detail the main processes responsible for the trafficking of copper and iron sulfur clusters, with particular interest for the structural aspects of the maturation of copper and iron-sulfur-binding proteins.