Background:The machinery for protein import into the mitochondrial intermembrane space has been studied in mammals, yeast, and plants. Results: Protist Erv homologues are conserved sulfhydryl:cytochrome c oxidoreductases with altered mechanisms. Conclusion:The composition and mechanism of the mitochondrial protein import machinery differs between eukaryotic lineages. Significance: The current knowledge on mitochondrial protein import cannot be generally transferred to all eukaryotes.

The Mia40/Erv1 disulfide relay system forms a structural disulfide bond in Ccs1, an unconventional substrate of this system. Thereby it promotes import of Ccs1 into mitochondria and controls its cellular distribution. Thus this system is unexpectedly able to form single disulfide bonds in complex multidomain proteins.