Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Abstract

Zinc is an essential trace element in humans. It is involved in numerous cellular processes and plays a role in the structural and catalytic functions of many cellular proteins. Therefore, its deficiency causes a myriad of pathophysiological symptoms in human patients. Recent studies have revealed that the number of people with marginal zinc deficiency has increased in Japan. Thus, zinc has started to receive great attention as a key factor for promoting good health.

Dietary zinc is absorbed in the intestine and then released into the bloodstream for delivery to the target tissues, including the liver. Many zinc transporters are expressed in the enterocytes and hepatocytes and known to be important for controlling systemic and cellular zinc homeostasis. In the enterocytes, ZIP4, located in the apical membrane, takes up dietary zinc from the intestinal lumen, whereas ZNT1, which is located in the basolateral membrane, releases the zinc into the portal blood. The expression of these transporters is dynamically regulated by zinc status. On the other hand, in the hepatocytes, ZIP14 plays a significant role in cellular zinc metabolism, and the expression level of this transporter is up-regulated by inflammation. In this review article, we briefly describe the mechanisms involved in the expression of zinc transporters, with a focus on the current progress towards understanding the roles of zinc transporters in zinc homeostasis and metabolism.