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

In a recent study published in Science , Tsvetkov et al 1 . 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.