Labile copper pool (LCP) (LCP)

The labile copper pool (LCP) refers to the fraction of intracellular copper that is loosely bound to low-molecular-weight ligands, such as glutathione and amino acids, making it readily available for biological processes [Ge et al., 2022; Faham et al., 2023]. Unlike the majority of cellular copper, which is tightly sequestered within metalloproteins, the LCP is dynamic and serves as a critical source for metallochaperones that deliver copper to essential enzymes like cytochrome c oxidase and superoxide dismutase [Blockhuys et al., 2017]. Maintaining the LCP within a narrow concentration range is vital, as copper is a potent redox-active metal that can catalyze the formation of reactive oxygen species via Fenton-like chemistry [Tsvetkov et al., 2022]. In diseases such as Wilson's disease, the LCP expands to toxic levels, leading to hepatic and neurological damage, whereas in many cancers, the pool is upregulated to support rapid proliferation and angiogenesis [European Association for the Study of the Liver, 2012; Blockhuys et al., 2017]. Pharmacological intervention targets the LCP through two primary strategies: chelation therapy to deplete the pool in cases of copper overload or cancer, and the use of copper ionophores to intentionally flood the pool and trigger cuproptosis, a copper-dependent form of regulated cell death [O'Day et al., 2013; Tsvetkov et al., 2022].

Other names

Exchangeable copper poolBioavailable copperRedox-active copperChelatable copperIntracellular copper pool

Modulation of intracellular copper levels via chelation to reduce bioavailability or ionophore-mediated transport to induce copper-dependent cytotoxicity (cuproptosis) [Tsvetkov et al., 2022; O'Day et al., 2013].