Mrp10 – A Regulator of Mitochondrial Protein Synthesis?

Most mitochondrial proteins are encoded in the nucleus, synthesized in the cytosol and imported into mitochondria. Proteins of the mitochondrial matrix typically carry N-terminal sequences which direct them into the matrix. Interestingly, many proteins of the mitochondrial intermembrane space (IMS) do not exhibit targeting sequences but conserved cysteine patterns named twin CX₃C and twin CX₉C motifs. These proteins are imported via oxidation of the cysteine residues mediated by Mia40.

During an initial characterization of the twin CX₉C protein family we identified Mrp10 as a potential substrate of Mia40. In contrast to other twin CX₉C proteins Mrp10 is located in the matrix and associated with ribosomes. Now, the question arises how a Mia40 substrate can be transported into the matrix. The amino acid sequence of Mrp10 shows properties of both ribosomal proteins and Mia40 substrates. In addition, Mrp10 possesses a proline-rich region in the N-terminus. We could show that this region serves as an uncommon matrix-targeting signal and that the import of Mrp10 into the matrix depends on the membrane potential.

Initial data indicate that the cysteines of Mrp10 are not required for import into the matrix but are crucial for the interaction with Mia40. We suggest that Mrp10 might have a dual localization and thus might be imported alternatively into the IMS (by Mia40) or into the matrix. Therefore, Mrp10 localization might be important for regulation of mitochondrial translation.