Fig. 1

Schematic diagram of Cu metabolism. A Cu absorption and transport in the body. Cu is absorbed by the body through the small intestine and subsequently released into the bloodstream. Hepatocytes in the liver then absorb and store the Cu from the blood. These liver cells can secrete Cu into the blood or bile. B Cu trafficking in mammalian cells. Outside mammalian cells, Cu ions are transported into the cell by the Cu ion transporter SLC31A1. Once inside the cell, these ions can bind to Cu chaperones in the cytoplasm, such as GSH, MT, ATOX1, and CCS1. ATOX1 is responsible for delivering Cu ions to ATP7A/B and trafficking them outside the cell via the TGN-associated endo/exocytosis. CCS1 delivers Cu ions to SOD1. Ligand-bound Cu ions (L-Cu) in the cytoplasm are transported to the mitochondrial intermembrane space, where they can be delivered to SOD1 via CCS1 or to SCO1 and COX11 via COX17. Alternatively, they can be transported into the mitochondrial matrix via SLC25A3. H3/H4 in the nucleus can reduce Cu²⁺ to Cu⁺