Fig. 2

Schematic of the cuproptosis mechanism. Cu⁺ is transported into the cells by SLC31A1. Cu²⁺ is transported into cells by Cu ionophores, including ES and DSF. The accumulated Cu binds to lipoylated DLAT, instigating its aggregation and triggering proteotoxic stress. FDX1 reduces Cu²⁺ to Cu⁺ and facilitates the lipoylation of DLAT. Cu inhibits FDX1-regulated synthesis of Fe–S clusters. This inhibition, combined with DLAT aggregation, leads to cell death. GSH and tetrathiomolybdate bind to Cu ions, restoring the level of free Cu ions and subsequently inhibiting cuproptosis