Dysregulation of copper metabolism and organelle-driven cellular injury: Mechanisms and therapeutic implications.

Copper is an essential trace element required for numerous physiological processes, with its systemic metabolism closely centered in the liver. This review systematically elucidates the mechanisms governing copper metabolism, emphasizing the pivotal roles of copper transporters and chaperone proteins in maintaining intracellular copper homeostasis. Furthermore, it examines how metabolic dysregulation of copper metabolism disrupts organelle function and drives cellular injury. Specifically, copper overload induces mitochondrial oxidative stress and cuproptosis, triggers endoplasmic reticulum stress responses and apoptosis, and compromises copper handling and excretion within the Golgi apparatus and lysosomes. These organelle-specific perturbations collectively contribute to cellular dysfunction and death. This review provides an integrated framework for understanding the pathogenesis of copper-related diseases and highlights potential therapeutic strategies targeting organelle-mediated copper homeostasis.