Fig. 5
From: Melanoma biology and treatment: a review of novel regulated cell death-based approaches
Schematic diagram of cuproptosis and correlation between cuproptosis and melanoma. Copper ions can cross the cell membrane into the intracellular space with a copper ionophore, and their concentration can be regulated by copper importers/exporters (SLC31A1/ATP7A and B). FDX1 not only reduces divalent copper to more toxic monovalent copper but also regulates protein lipoylation. Intracellular copper can bind lipoylated proteins directly, leading to their aggregation and further occurrence of cuproptosis. Copper ions also contribute to Fe-S cluster loss, which is another mechanism of cuproptosis. Related researches are expressed in white squares with reference number in parenthesis. Elesclomol, a copper ionophore, can induce cuproptosis, and was shown to eliminate slow-cycling melanoma cells. A higher expression level of LIPT1, responsible for transferring lipoic acid to the E2 subunits of AKGDH and pyruvate dehydrogenase PDH, is related to longer survival after immunotherapy