Distinct signaling mechanisms and proteome phenotypes are elicited by compartment-specific genetic defects of copper homeostasis.

ABSTRACT: Impairments to the complex machinery regulating copper homeostasis lead to neurodevelopmental diseases, demonstrating the importance of copper for neuronal health and maintenance. The exact mechanisms by which the brain responds to copper deficiency following disruptions to the copper transporters ATP7A and CTR1 in conditions such as Menkes disease remain unclear, though failure to supply complex IV of the respiratory chain with copper is suspected to account for substantial pathology. Here, we studied mechanisms of copper deficiency using systems biology approaches to contrast isogenic CTR1- and COX17-deficient cells, which model copper deficiency at the level of the whole cell or complex IV, respectively. Multiomics approaches revealed distinct signaling mechanisms elicited by compartmen

SUBMITTER: Lane AR 

PROVIDER: S-EPMC12871135 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature