Cuproptosis:lipoylated TCA cycle proteins-mediated novel cell death pathway

In a recent study published in Science,Tsvetkov et al1.shed a light on a new form of cell death,copper-dependent cell death(termed cuproptosis).They defined“cuproptosis”as a nonapoptotic cell death pathway.They have demonstrated that copper directly binds to lipoylated components of the tricarboxylic acid(TCA)cycle.Then aggregation of these copper-bound,lipoylated mitochondrial proteins and subsequent Fe-S cluster protein loss triggered proteotoxic stress and a distinct form of cell death.