Cytochrome c oxidase assembly factor SCO1

SCO1 is a copper metallochaperone protein essential for the maturation of cytochrome c oxidase subunit II (MT-CO2/COX2), a critical component of mitochondrial respiratory complex IV (UniProt: O75880). Working alongside SCO2, SCO1 delivers copper to the Cu(A) site on MT-CO2/COX2 and helps regulate copper homeostasis by controlling the abundance and localization of the copper transporter CTR1. The protein is 301 amino acids long and highly conserved.

SCO1 is localized to mitochondria, where it functions in oxidative phosphorylation and energy metabolism. Pathogenic variants in SCO1 cause mitochondrial complex IV deficiency, an autosomal recessive disorder presenting with severe neurological and cardiac manifestations in infancy (UniProt: O75880).

In Alzheimer's Disease, SCO1 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.71 across one subcellular fraction from TMT-labeled quantitative proteomics (Chaparral AD proteomics). This elevation may reflect compensatory mitochondrial stress responses or altered energy metabolism in the AD brain, though the functional significance requires further investigation.