The Janus face of copper: its expanding roles in biology and the pathophysiology of disease. Meeting on Copper and Related Metals in Biology.

Introduction Copper is an essential cofactor for several enzymes that catalyse many biochemical reactions crucial for normal cell physiology. Its ability to accept and donate single electrons as it changes oxidation state between Cu+ and Cu2+—that is, Cu(I) and Cu(II), respectively— makes copper an ideal biological cofactor; however, this ability also allows it to readily catalyse the formation of reactive oxygen species (ROS) through Fenton chemistry when unbound within the cell. Several specific trafficking pathways have evolved to ensure that most copper ions in the cell are either compartmentalized or protein bound, thereby maximizing the trade-off between their biological utility and toxicity. These pathways include Cu(I)-binding metallochaperones that shuttle copper to different subcellular sites for storage or the assembly of cupro-enzymes, and copper permeases and effluxers that act in a coordinated manner to modulate intracellular copper concentration within a relatively narrow range. The Alghero conference highlighted progress in characterizing the function of copper permeases and the molecular genetic regulation of cellular copper levels. The importance of copper in neurobiology and the etiology of several neurological syndromes were also addressed, together with exciting new discoveries that link copper to both the immune response and programmed cell death.