Copper in mammals: mechanisms of homeostasis and pathophysiology

The ability of mammals to tightly regulate systemic copper levels is vital for
health as demonstrated by the severity of the genetic copper deficiency and copper toxicity disorders, Menkes disease and Wilson disease, respectively. Analysis of these genetic disorders has led to a substantial increase in the understanding of the role of copper in health and disease. The isolation of the genes involved in these diseases and use of yeast mutants with altered copper and iron homeostasis has revealed a range of molecular mechanisms governing copper homeostasis. These mechanisms include regulation of cellular copper uptake and efflux and involve the use of chaperones for safe intracellular copper distribution. Here we provide an overview of the physiological role of copper and the molecular mechanisms
regulating systemic and cellular copper levels in mammals. Furthermore, we discuss the pathophysiological mechanisms and consequences of copper deficiency/overload in relation to disease.