Fig. 3: Schematic of cuproptosis mechanism.
From: Copper homeostasis and cuproptosis in central nervous system diseases
Extracellular Cu is bound by Cu ionophores like elesclomol and moved into intracellular compartments. Cu then attaches itself to lipoylated mitochondrial TCA cycle enzymes, like DLAT, causing these proteins to aggregate. As the upstream regulator of protein lipoylation, FDX1/LIAS promotes the loss of Fe-S clusters and the aggregation of mitochondrial proteins. These aberrant processes ultimately result in cell demise via proteotoxic stress. Copper chelators such as GSH inhibit cuproptosis.
