Copper homeostasis and cuproptosis in health and disease

As an essential micronutrient, copper is required for a wide range of physiological processes in virtually all cell types. Because the accumulation of intracellular copper can induce oxidative stress and perturbing cellular function, copper homeostasis is tightly regulated. Recent studies identified a novel copper-dependent form of cell death called cuproptosis, which is distinct from all other known pathways underlying cell death. Cuproptosis occurs via copper binding to lipoylated enzymes in the tricarboxylic acid (TCA) cycle, which leads to subsequent protein aggregation, proteotoxic stress, and ultimately cell death. Here, we summarize our current knowledge regarding copper metabolism, copper-related disease, the characteristics of cuproptosis, and the mechanisms that regulate cuproptosis. In addition, we discuss the implications of cuproptosis in the pathogenesis of various disease conditions, including Wilson's disease, neurodegenerative diseases, and cancer, and we discuss the therapeutic potential of targeting cuproptosis.

Automated summary

Copper is an essential micronutrient that is required for various physiological processes in almost all cell types, and its homeostasis is tightly regulated to avoid oxidative stress and cellular dysfunction. Recent studies have identified a novel form of cell death called cuproptosis, which is induced by copper binding to lipoylated enzymes in the tricarboxylic acid cycle and ultimately leads to protein aggregation, proteotoxic stress, and cell death. This article summarizes current knowledge on copper metabolism, copper-related diseases, the characteristics of cuproptosis, and the regulatory mechanisms involved. The implications of cuproptosis in the pathogenesis of diseases such as Wilson's disease, neurodegenerative diseases, and cancer are also discussed, along with the therapeutic potential of targeting cuproptosis.