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Metals and other trace elements play an important role in many physiological processes in all biological systems. Characterization of precise metal concentrations, their spatial distribution, and chemical speciation in individual cells and cell compartments will provide much needed information to explore the metallome in health and disease. Synchrotron-based X-ray fluorescent microscopy (SXRF) is the ideal tool to quantitatively measure trace elements with high sensitivity at high resolution. SXRF is based on the intrinsic fluorescent properties of each element and is therefore element specific. Recent advances in synchrotron technology and optimization of sample preparation have made it possible to image metals in mammalian tissue with submicron resolution. In combination with correlative methods, SXRF can now, for example, determine the amount and oxidation state of trace elements in intra-cellular compartments and identify cell-specific changes in the metal ion content during development or disease progression.

Copper-transporting ATPase ATP7B (Wilson disease protein) is a member of the P-type ATPase family with characteristic domain structure and distinct ATP-binding site. ATP7B plays a central role in the regulation of copper homeostasis in the liver by delivering copper to the secretory pathway and mediating export of excess copper into the bile. The dual function of ATP7B in hepatocytes is coupled with copper-dependent intracellular relocalization of the transporter. The final destination of ATP7B in hepatocytes during the copper-induced trafficking process is still under debate. We show the results of immunocytochemistry experiments in polarized HepG2 cells that support the model in which elevated copper induces trafficking of ATP7B to sub-apical vesicles, and transiently to the canalicular membrane. In Atp7b-/- mice, an animal model of Wilson disease, both copper delivery to the trans-Golgi network and copper export into the bile are disrupted despite large accumulation of copper in the cytosol. We review the biochemical and physiological changes associated with Atp7b inactivation in mouse liver and discuss the pleiotropic consequences of the common Wilson disease mutation, His1069Gln.