The Tao of Copper Metabolism: From Physiology to Pathology

As a transitional metal, copper plays a crucial role in maintaining the normal physiological activities of mammals. The intracellular copper concentration is meticulously regulated to maintain extremely low levels through homeostatic regulation. Excessive accumulation of free copper in cells can have deleterious effects, as observed in conditions such as Wilson's disease. Moreover, data accumulated over the past few decades have revealed a crucial role of copper imbalance in tumorigenesis, progression and metastasis. Recently, cuproptosis, also known as copper-induced cell death, has been proposed as a novel form of cell death. This discovery offers new prospects for treating copperrelated diseases and provides a promising avenue for developing copper-responsive therapies, particularly in cancer treatment. We present a comprehensive overview of the Yin- Yang equilibrium in copper metabolism, particularly emphasising its pathophysiological alterations and their relevance to copper-related diseases and malignancies.