Elesclomol rescues mitochondrial copper deficiency in disease models without triggering cuproptosis.

ABSTRACT: Copper (Cu) is an essential cofactor for metalloenzymes such as cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial electron transport chain. Mutations that directly or indirectly prevent Cu transport to mitochondria result in lethal pediatric diseases, such as Menkes disease. There is no clinically approved treatment for Menkes disease. We recently discovered that an investigational chemotherapy drug, elesclomol (ES), when complexed with Cu (ES-Cu), rescues mitochondrial Cu deficiency, activates CcO, and prevents perinatal lethality in a mouse model of Menkes disease. However, ES-Cu also has the potential to trigger cuproptosis, a type of Cu-dependent cell death. Therefore, to develop ES-Cu as a therapeutic agent for Menkes disease, it is critical to determine the therape

SUBMITTER: Zulkifli M 

PROVIDER: S-EPMC12718110 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature