Human deafness dystonia syndro

The human deafness dystonia syndrome re- sults from the mutation of a protein (DDP) of unknown function. We show now that DDP is a mitochondrial protein and similar to five small proteins (Tim8p, Tim9p, TimlOp, Timl2p, and Timl3p) of the yeast mitochondrial intermem- brane space. Tim9p, TimlOp, and Timl2p mediate the import of metabolite transporters from the cytoplasm into the mito- chondrial inner membrane and interact structurally and functionally with Tim8p and Timl3p. DDP is most similar to Tim8p. Tim8p exists as a soluble 70-kDa complex with Timl3p and Tim9p, and deletion of Tim8p is synthetically lethal with a conditional mutation in TimlOp. The deafness dystonia syndrome thus is a novel type of mitochondrial disease that probably is caused by a defective mitochondrial protein- import system.