Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.

ABSTRACT: Rare inherited diseases caused by mutations in the copper transporters SLC31A1 (CTR1) or ATP7A induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation. Proteomic and transcriptomic analysis of CTR1 knockout (KO) cells revealed simultaneous up-regulation of mTORC1 and S6K signaling and reduced PERK signaling. Patterns of gene and protein expression and pharmacogenomics show increased activation of the mTORC1-S6K pathway a

SUBMITTER: Lane AR 

PROVIDER: S-EPMC11974963 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature