Copper and cuproptosis: mechanisms, biology, and roles in disease.

作者：Fudi Wang, Wenye Liu, C. Tao, Li-Yun Chen, Ningjun Ni, Liujing Huang, Yueyang Ouyang, Qianqian Shi, Dandan Wu, Chenghua Li, Liwei Xie, Yanfang Wang, Junxia Min, Jing-Xia Liu · 发表于：Science Bulletin · 年份：2026 · DOI：10.1016/j.scib.2026.05.007 · 被引用次数：2 · 研究领域：Medicine

Copper, an evolutionarily conserved redox-active trace element, serves as an irreplaceable core pillar of eukaryotic life-orchestrating cuproenzyme catalysis, metabolic signaling networks, and organelle homeostasis across molecule-to-organism scales. Its strict homeostasis is a prerequisite for physiological function, and its dysregulation is a hallmark of diverse pathologies. The discovery of cuproptosis-a distinct mitochondria-centric programmed cell death-has fundamentally upended traditional paradigms of metal-mediated cytotoxicity. Cuprology, serves as an integrative interdisciplinary framework to unify copper's spatiotemporal regulation across biological hierarchies. This inherent duality governs health and disease: physiological copper sustains developmental metabolism and redox balance, while deficiency or overload drives pathogenesis spanning metabolic disorders, neurodegeneration, and cancer. Integrating foundational mechanistic insights with cutting-edge translational breakthroughs-from copper ionophores to nano-carrier-mediated precision delivery. This review synthesizes the intricate crosstalk between copper homeostasis, cuproptosis circuitry, and cellular metabolism under the Cuprology framework. It further charts a clear roadmap for targeting copper-cuproptosis axes, unlocking transformative therapeutic strategies for recalcitrant diseases and steering a new era of research into cell death and metabolic regulation.