Fig. 2

Schematic of systemic and cellular copper metabolism. The body absorbs copper mostly through the small intestine, where it is then transported by blood to the liver for excretion into the bile. In tumor cells, interactions between several proteins maintain copper homeostasis. The entry and departure of copper ions into and out of the cell are controlled by the copper ion transporters SLC31A1 and ATP7B, whereas the transit of copper ions through the outer and inner mitochondrial membranes is controlled by COX17 and SLC25A3, respectively. Copper ions entering the cytoplasm and mitochondrial intermembrane space bind to GSH and MT or form copper-containing molecular chaperones such as SOD1 which is crucial for proper function of copper. To sustain normal cellular functions, COA6, SCO1 and SCO2 work together to mediate the transfer of copper to COX in the mitochondrial intermembrane space