Abstract
Sco1 and Sco2 are mitochondrial copper metallochaperones specific for cytochrome c oxidase (CcO). Both proteins are presumably involved in copper transfer/insertion into the CuA center of CcO subunit Cox2.
In this paper we analyzed the impact on CcO assembly and tissue copper levels of a G132S mutation in the juxtamembrane region of SCO1 metallochaperone associated with early onset hypertrophic cardiomyopathy, encephalopathy, hypotonia, and hepatopathy, assessed the total copper content of various SURF1 and SCO2-deficient tissues, and investigated the possible physical association between CcO and Sco1. We found that the G132S mutation compromises the stability of the mutant protein, presumably by its impaired ability to dimerize.
Similarly to Sco1 and Sco2-deficient tissues, also the samples affected by mutations in another CcO-specific assembly protein Surf1 showed marked defect of total cellular copper. Finally, both co-purification and blue-native western blotting demonstrated that a significant fr