Redox-active copper pool (RCP)

The redox-active copper pool, also known as the labile copper pool, refers to the fraction of intracellular copper ions that are loosely bound to low-molecular-weight ligands and are readily available for biochemical reactions (Tsvetkov et al., Science, 2022). This pool is distinct from copper sequestered within the active sites of metalloproteins and is essential for maintaining cellular homeostasis by providing copper for mitochondrial respiration and antioxidant enzymes (Ge et al., Nature Chemical Biology, 2022). However, an excess of redox-active copper can lead to toxicity through the generation of reactive oxygen species via Fenton-like chemistry or by triggering cuproptosis, a regulated cell death pathway involving the aggregation of lipoylated proteins (Tsvetkov et al., Science, 2022). In many cancers, the redox-active copper pool is expanded to support rapid proliferation, signaling, and angiogenesis, making it a significant therapeutic target (Brady et al., Nature, 2014). Therapeutic strategies include the use of copper chelators like tetrathiomolybdate to deplete the pool and copper ionophores like elesclomol to overload the pool and induce selective cell death in malignant cells (Blockhuys et al., Journal of Trace Elements in Medicine and Biology, 2017). Monitoring this pool is critical in managing copper-related disorders such as Wilson disease and in the development of novel copper-dependent anti-cancer agents.

Other names

Labile copper poolExchangeable copper poolBioavailable copperIntracellular copper poolCu(I)/Cu(II) pool

Modulation of intracellular copper levels via chelation to deplete copper or ionophore-mediated transport to induce copper-dependent cell death (cuproptosis).