Intracellular copper pool (ICP)

The intracellular copper pool refers to the fraction of copper within a cell that is not irreversibly bound to metalloproteins but is instead associated with low-molecular-weight ligands or chaperones. This pool is chemically labile and serves as a critical reservoir for the maturation of essential enzymes involved in cellular respiration, antioxidant defense, and neurotransmitter synthesis (Tsvetkov et al., 2022, Science). Under normal physiological conditions, copper concentrations are tightly regulated by transporters like CTR1 and ATP7A/B to prevent oxidative damage. In pathological states such as Wilson's disease, the expansion of this pool leads to mitochondrial dysfunction and proteotoxic stress (NIH, 2023). Conversely, cancer cells often exhibit an increased requirement for copper, making the pool a target for copper-dependent cell death, or cuproptosis. Therapeutic strategies include the use of chelators like D-penicillamine to sequester and excrete excess copper in overload disorders (PubChem). Additionally, copper ionophores such as elesclomol are being investigated for their ability to shuttle copper into mitochondria to induce cuproptosis in malignant cells. Monitoring this pool is vital, as excessive depletion can lead to systemic copper deficiency, manifesting as anemia or neurological impairment.

Other names

Labile copper poolExchangeable copper poolCytosolic copper poolBioavailable copper pool

Drugs targeting the intracellular copper pool primarily act through chelation to facilitate the excretion of excess copper or via ionophores that transport copper into cells to trigger cuproptosis or restore copper-dependent enzyme activity.