Fig. 1.

Overview of systemic and cellular copper homeostasis.

The human body primarily absorbs copper through the small intestine, which is then transported to the liver via the bloodstream and excreted into bile. CP serves as the main protein carrier for exchangeable copper in the blood plasma, while excess copper is stored in hepatocytes by MT1 and MT2. At the cellular level, the metal reductase STEAP and the copper transporter CTR1 enable high-affinity copper uptake. Copper is transported to different subcellular organelles through various copper-binding proteins, such as COX17, CCS, and ATOX1. These proteins play a crucial role in ensuring the availability of copper within the cell. Ultimately, ATP7A and ATP7B transfer copper from the cytosol to the TGN lumen. When intracellular copper levels are high, ATP7A and ATP7B exit the TGN, facilitating the efflux of copper from the cell. CP, ceruloplasmin; MT1, metallothionein 1; STEAP, six-transmembrane epithelial antigen of the prostate; CTR1, copper transporter 1; COX17, cytochrome C oxidase copper chaperone 17; CCS, copper chaperone for superoxide dismutase; ATOX1, antioxidant-1; SOD1, superoxide dismutase 1; SCO1, synthesis of cytochrome c oxidase 1; COX11, cytochrome C oxidase copper chaperone 11; CCO, cytochrome C oxidase; ATP7A, ATPase Copper Transporting Alpha; TGN, trans-Golgi network.