Fig. 3.

The putative role of cuproptosis in Wilson’s disease. a Patients with Wilson’s disease present with Cu overload in their hepatocytes. Mutations in ATP7B impair Cu loading into secretory vesicles and into cuproproteins such as ceruloplasmin. Cu excretion via the biliary tract is also impaired, resulting in an accumulation of Cu in the liver. The resulting Cu-induced toxicity leads to chronic liver disease and cirrhosis. Cu also accumulates in other tissues, including the brain, cornea, and kidneys, resulting in neurological impairment, Kayser–Fleischer rings, and impaired kidney function, respectively. b Atp7b knockout mice (a model of Wilson’s disease) develop Cu overload, with a loss of lipoylated and Fe–S cluster proteins in the liver, suggesting that this Cu overload has similar cellular effects as those induced by Cu ionophores, suggesting that cuproptosis may play a pathogenic role in Wilson’s disease. Created with BioRender. ATOX1 antioxidant 1 copper chaperone-1, ATP7B ATPase Cu transporter 7B, Fe–S iron–sulfur, Slc3a1 solute carrier family 3 member 1, STEAP six-transmembrane epithelial antigen of prostate