Fig. 4: Schematic diagram of the mechanisms of cuproptosis. | Cell Death Discovery

Fig. 4: Schematic diagram of the mechanisms of cuproptosis.

From: Copper homeostasis and cuproptosis in atherosclerosis: metabolism, mechanisms and potential therapeutic strategies

Fig. 4

The copper ionophore ES transports extracellular copper into the cell. Subsequently, intracellular copper binds to lipoylated mitochondrial enzymes (such as DLAT) involved in the TCA cycle. This binding leads to the aggregation of these proteins, which can disrupt the TCA cycle and, therefore, interfere with cellular energy production. The upstream regulatory factors FDX1 and LIAS play a critical role in this process. The aggregation of lipoylated mitochondrial proteins and loss of Fe-S clusters promote proteotoxic stress and ultimately lead to cell death. Figure created with BioRender. SLC31A1 solute carrier family 31 member 1, STEAP the six-transmembrane epithelial antigen of the prostate, ATP7A and ATP7B ATPase copper transporter 7A and 7B, ES elesclomol, α-KG α-ketoglutarate, DLAT dihydrolipoamide S-acetyltransferase, FDX1 ferredoxin-1, Fe–S iron–sulfur, LIAS lipoic acid synthetase, TCA tricarboxylic acid, and GSH glutathione.

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