Copper homeostasis and its dysregulation in diseases: A focus on cuproptosis

Abstract

Copper, an essential trace element, orchestrates diverse cellular metabolic processes through tightly regulated homeostasis. Intracellular copper homeostasis, governed by key regulators such as the copper transporter 1 (CTR1), is critical for maintaining physiological functions. Dysregulation of copper homeostasis, whether resulting in deficiency or overload, constitutes a central driver of disease pathogenesis. Notably, copper overload induces cuproptosis, a novel form of programmed cell death that has recently emerged as a promising therapeutic target across multiple diseases. Deciphering the regulatory mechanisms of cuproptosis may unlock new avenues for targeted therapy development. This review delves into the mechanisms of copper homeostasis and the pathogenic consequences of its imbalance, with a particular emphasis on cuproptosis-based strategies for cancer treatment.