Cuproptosis: A Copper-Mediated Programmed Cell Death

It has been found that various heavy metals can initiate different types of regulated cell deaths. Among these metals, copper, an essential trace micronutrient that plays a major role in a lot of physiological processes, also can initiate cell death. It can act as a constituent of metalloenzymes, and can act as a mediator for signaling pathways to regulate proliferation and metastasis of tumor. It is also an integral part of some metal-based anticancer drugs. Recent studies have revealed that excessive intracellular copper accumulation leads to the aggregation of mitochondrial lipoylated proteins, causing proteotoxic stress and ultimately resulting in cell death. This newly discovered copper-induced cell death is termed as cuproptosis. In the last few years, a lot of research has been done to understand the mechanism of copper-mediated cell death, and attempts have also been made to identify the relationship between cuproptosis and the development of cancer. In this review, we have provided a comprehensive overview on the significance of copper, its regulation inside the body, the possible mechanism of cuproptosis, and how this cuproptosis can be employed as a therapeutic tool for cancer ablation.