fig3

Figure 3. The mechanism of cuproptosis. Copper ionophore elesclomol directly transports Cu²⁺ into cells and then Cu²⁺ is reduced to Cu⁺ via FDX1. After the reduction of Cu²⁺ into Cu⁺ via STEAP, Cu⁺ is pumped into cells via SLC31A1. FDX1 and LIAS induce DLAT lipoylation and aggregation, inducing the damage of the TCA cycle. As such, cells are dead via cuproptosis. FDX1: Ferredoxin 1; STEAP: 6-transmembrane epithelial antigen of prostate, comprises STEAP1, STEAP2, STEAP3, and STEAP4; SLC31A1: solute carrier family 31 member 1; LIAS: lipoic acid synthetase; DLAT: dihydrolipoamide S-acetyltransferase; TCA: tricarboxylic acid; LA: lipoic acid.