Figure 2.

Control of cellular zinc homeostasis including regulation of zinc and functions of zinc in regulation. (1) Tier 1: cellular homeostasis through import and export through the plasma membrane and subcellular distribution; (2) Tier 2: vesicular storage and/or release of zinc associated with zinc importers and exporters on the vesicles; (3) Tier 3: loading of secretory vesicles with zinc associated only with zinc exporters on the vesicles. Regulatory functions of zinc require additional complexity in homeostatic control, namely, molecules that control the spatiotemporal fluctuations of zinc ions in a metal-buffered environment, above the fluxes in re-distributing zinc for supply as a cofactor in catalytic and structural sites of proteins. With this distinction, we assume that the functions of bona fide zinc proteins are not regulated by zinc coming on and off from their catalytic and structural sites. (Figures were composed from Servier Medical Art templates (http://smart.servier.com/)).