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Free Copper Ions in the Cell?

How enzymes such as copper-zinc superoxide dismutase (SOD1), an important antioxidant enzyme in the cell, obtain the transition metal ions that they need to function is still far from understood. In
 Science this week,
 Rae
 et al . demonstrate that the yCCS metallochaperone in yeast inserts copper ions directly into the enzyme and is only active at very low concentrations of intracellular copper. Moreover, these investigators made the unexpected discovery that there is less than one atom of free copper per cell. A Perspective by
 Lippard
 comments on these findings and their implications for human diseases that involve dysregulation of transition metal ion intracellular concentrations or mutations in SOD1.