Cytochrome c oxidase assembly factors with a thioredoxin fold are conserved among prokaryotes and eukaryotes

Cytochrome c oxidase (COX) is a multi-subunit terminal oxidase of the eukar yotic respiratory chain involved in the reduction of oxygen to water. Numer ous lines of evidence suggest that the assembly of COX is a multi-step, ass isted process that depends on several assembly factors with largely unknown functions. Sco1/2 proteins have been isolated as high-copy number suppress ors of a deletion of copper chaperone Cox17, implicating Sco1/2 in copper t ransport to COX subunits I or II. Here I report the similarity of Sco1/2 as sembly factors to peroxiredoxins and thiol:disulfide oxidoreductases with a thioredoxin fold, suggesting that Sco-related proteins perform a catalytic rather than a copper transport function. Reported sequence similarities, t ogether with the functional role of bacterial Sco-related proteins suggest that Sco-related proteins represent a new class of membrane-anchored thiol: disulfide oxidoreductases involved in COX maturation.