Qiu, Yijian, Lukey, Michael J (October 2026) Cuproptosis and the bioinorganic basis of copper-induced cell death. Journal of Biological Inorganic Chemistry. ISSN 1432-1327
Abstract
Copper is an essential yet potentially toxic biological trace element, whose functions in cells arise from its unique redox and coordination chemistry. The same chemical properties that make copper indispensable for a variety of fundamental biological processes, including respiration and antioxidant defense, also render it highly toxic when intracellular concentrations exceed homeostatic levels. Recently, a copper-dependent form of regulated cell death (RCD) termed cuproptosis has been identified, in which excess copper triggers cytotoxicity by directly binding the metabolic machinery of mitochondria to induce proteotoxic stress. Hallmark features of cuproptosis include the high-affinity coordination of copper with lipoylated proteins and the destabilization of iron-sulfur (Fe-S) cluster enzymes within the mitochondrial matrix, which together trigger metabolic dysfunction and protein aggregation that ultimately lead to cell death. Cuproptosis thus represents the first RCD pathway whose execution depends directly on metal-protein coordination chemistry. Emerging evidence indicates that cuproptosis may contribute to the pathogenesis of a variety of human diseases including cancer, neurodegeneration, and genetic disorders of copper metabolism. A precise mechanistic understanding of this form of RCD therefore has the potential to reveal new opportunities for therapeutic intervention. Here, we examine the bioinorganic basis of cuproptosis, its intersections with cellular copper handling systems, its role in disease processes, and the potential therapeutic strategies that aim to exploit this pathway for clinical benefit.
| Item Type: | Paper |
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| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell death organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Lukey lab CSHL Post Doctoral Fellows |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 5 October 2026 |
| Date Deposited: | 13 Oct 2026 12:20 |
| Last Modified: | 13 Oct 2026 12:20 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/42338 |
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