Human deafness dystonia syndrome is a mitochondrial disease

The human deafness dystonia syndrome results 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, Tim10p, Tim12p, and Tim1 3p) of the yeast mitochondrial intermembrane space. Tim9p, Tim10p, and Tim1 2p mediate the import of metabolite transporters from the cytoplasm into th e mitochondrial inner membrane and interact structurally and functionally w ith Tim8p and Tim13p. DDP is most similar to Tim8p. Tim8p exists as a solub le 70-kDa complex with Tim13p and Tim9p, and deletion of Tim8p is synthetic ally lethal with a conditional mutation in Tim10p. The deafness dystonia sy ndrome thus is a novel type of mitochondrial disease that probably is cause d by a defective mitochondrial protein-import system.