Fig. 1.

ELC transfers copper (Cu²⁺) from the extracellular matrix to intracellular compartments by binding to it. Cuproptosis is primarily brought on by increased Cu buildup and mitochondrial proteotoxic stress, which is mediated by FDX1. On one hand, FDX1 facilitates the lipoylation (LA) and aggregation of enzymes (particularly DLAT) involved in the control of mitochondrial TCA cycle by reducing Cu²⁺ to Cu⁺. On the other hand, FDX1 facilitates lipoylation and aggregation of enzymes that control the mitochondrial TCA cycle (particularly DLAT) by reducing Cu²⁺ to Cu⁺