Copper in Eukaryotes
Copper is essential for normal growth and development of eukaryotic organisms. Numerous physiological processes rely on sufficient availability of copper: from indispensable reactions such as mitochondrial respiration to more highly specialized processes such as pigment development in a skin. Copper misbalance has been linked to a variety of metabolic and neurodegenerative disorders in humans. Complex cellular machinery has evolved to mediate copper uptake, compartmentalization and incorporation into target proteins. Extensive studies revealed a predominant utilization of methionines and histidines by copper handling molecules for copper capture at the extracellular surface and delivery to cuproenzymes in the lumen of cellular compartments, respectively. Cu(I) is a predominant form within the cell, and copper binding and distribution inside the cell at the cytosolic sites relies heavily on cysteines. The selectivity and directionality of copper transfer reactions is determined by thermodynamic and kinetic factors as well as spatial distribution of copper donors and acceptors. In this chapter, we review current structural and mechanistic data on copper transport and distribution in yeast and mammalian cells and highlight important issues and questions for future studies.