Elemental selectivity and homeostatic crosstalk among zinc, copper, and manganese in vertebrate cells

Zinc (Zn), Copper (Cu), and Manganese (Mn) are micronutrients that are essential for biological functions. They act as cofactors for numerous proteins and serve as signaling molecules. Although recent studies have significantly advanced our understanding of the individual roles of these metals, their homeostatic interactions remain largely unclear, except for a few well-documented cases, most notably the well-known competition between Zn and Cu for intestinal absorption. Moreover, recent research in vertebrates has suggested that Mn metabolism is closely linked to Zn metabolism in various cellular processes. Investigating the regulatory mechanisms governing homeostasis of essential trace metals is crucial for elucidating their functions in cellular systems. In this review, we provide a brief overview of the recent advances in understanding the competition between Cu, Mn, and Zn, with a particular focus on the interaction of Zn with the other two metals.