Cytochrome c oxidase (COX) complex is built up with both nucleus- and mitochondrion-encoded subunits. Biogenesis and assembly of the complex thus requires fine cross-talk between the two compartments. In order to shed light on the regulation of nuclear–mitochondrial interactions, we studied the expression of COXIII (mitochondrion-encoded) and COXIV (nucleus-encoded) in adult rat tissues and rat developing brain. We found that the levels of COXIV protein and mRNA are not linearly related, thus suggesting a post-transcriptional mode of regulation. In agreement with this observation, we report the presence of a protein that specifically binds to the 3′-untranslated region of COXIV mRNA. This factor, that forms with RNA a complex of about 60 kDa, is present both in the cytoplasm and mitochondria, where its concentration decreases throughout development with inverse correlation with COXIV accumulation. Interestingly, using an antibody raised in our laboratory, we found that, in developing rat brain, COXIII does not localize exclusively to mitochondria, but is also present in the cytosol, where it could exert a yet unknown regulatory role.