Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Zinc is involved in virtually all aspects of cellular and molecular biology as a catalytic, structural, and regulatory cofactor in over 1000 proteins. Zinc binding to proteins requires an adequate supply of zinc and intact molecular mechanisms for redistributing zinc ions to make them available at the right time and location. Several dozen gene products participate in this process, in which interactions between zinc and sulfur donors determine the mobility of zinc and establish coupling between cellular redox state and zinc availability. Specifically, the redox properties of metallothionein and its apoprotein thionein are critical for buffering zinc ions and for controlling fluctuations in the range of picomolar concentrations of "free" zinc ions in cellular signaling. Metallothionein and other proteins with sulfur coordination environments are sensitive to redox perturbations and can render cells susceptible to injury when oxidative stress compromises the cellular redox and zinc buffering capacity in chronic diseases. The implications of these fundamental principles for zinc metabolism in type 2 diabetes are briefly discussed.