1. Department of Obstetrics and Gynaecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
2. Institute of BioPharmaceutical sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
3. Department of Obstetrics and Gynaecology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
4. Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
5. Department of Surgery, Kaohsiung Municipal Minsheng Hospital, Kaohsiung, Taiwan.
6. Institute of Physiological Chemistry and Pathobiochemistry and Cells in Motion Interfaculty Centre (CiMIC), University of Münster, 48149 Münster, Germany.
7. Institute of Clinical Medicine, National Cheng Kung University, Tainan 704, Taiwan.
8. Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
9. Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
10. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
# Equal contribution.
Copper (Cu) plays a crucial and diverse function in biological systems, acting as a cofactor at numerous sites of enzymatic activity and participating in various physiological processes, including oxidative stress regulation, lipid metabolism, and energy metabolism. Similar to other micronutrients, the body regulates Cu levels to ensure homeostasis; any disruption in Cu homeostasis may result in various illnesses. Cuproptosis causes proteotoxic stress and ultimately results in cell death by the binding of Cu ions to lipid-acylated proteins during the tricarboxylic acid cycle of mitochondrial respiration. Cu is not only involved in regulatory cell death (RCD), but also in exogenous factors that induce cellular responses and toxic outcomes. Cu imbalances also affect the transmission of several RCD messages. Therefore, this article presents a thorough examination of the mechanisms involved in Cu-induced RCD as well as the role of Cu complexes in its pathophysiology.
Keywords: Copper, Cuproptosis, Regulatory cell death, Pathophysiology