Labile copper pool (LCP)

The labile copper pool (LCP) represents a small, dynamic fraction of intracellular copper that is loosely bound to low-affinity ligands such as glutathione and small organic acids. Unlike the majority of cellular copper, which is safely sequestered within metalloproteins or chaperones, the LCP is redox-active and readily exchangeable, making it both essential for metabolic signaling and potentially toxic. Pathological expansion of this pool leads to the generation of reactive oxygen species via Fenton-like chemistry and can trigger cuproptosis, a copper-dependent form of regulated cell death characterized by the aggregation of lipoylated mitochondrial proteins (Tsvetkov et al., 2022, Science). In clinical practice, the LCP is targeted by chelating agents to treat copper overload disorders like Wilson disease or by copper ionophores to selectively induce cell death in copper-dependent cancers (Kahlson & Dixon, 2022, Nature Chemical Biology). Monitoring the LCP via biomarkers like non-ceruloplasmin bound copper is critical for managing copper homeostasis and evaluating the efficacy of copper-modulating therapies in clinical settings (Faham et al., 2021, Nutrients).

Other names

Exchangeable copper poolBioavailable copperRedox-active copperPathological copper poolLabile intracellular copperNon-protein-bound copper

Chelation of exchangeable copper to facilitate urinary excretion; Ionophore-mediated transport of copper into mitochondria to induce proteotoxic stress and cuproptosis; Induction of endogenous copper-binding proteins like metallothionein to sequester labile ions.