Copper serves as the essential cofactor for a number of enzymes involved in redox chemistry and virtually all organisms must accumulate trace levels of copper in order to survive. However, this metal can also be toxic and a number of effective methods for sequestering and detoxifying copper prevent the metal from freely circulating inside a cell. Copper metalloenzymes are therefore faced with the challenge of acquiring their precious metal cofactor in the absence of available copper. To overcome this dilemma, all eukaryotic organisms have evolved with a family of intracellular copper binding proteins that help reserve a bioavailable pool of copper for the metalloenzymes, escort the metal to appropriate targets, and directly transfer the copper ion. These proteins have been collectively called "copper chaperones." The identification of such molecules has been made possible through molecular genetic studies in the bakers' yeast Saccharomyces cerevisiae. In this review, we highlight the findings that led to a new paradigm of intracellular trafficking of copper involving the action of copper chaperones. In particular, emphasis will be placed on the ATX1 and CCS copper chaperones that act to deliver copper to the secretory pathway and to Cu/Zn superoxide dismutase in the cytosol, respectively.
ASJC Scopus subject areas
- Cell Biology