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 Tim13p) of the yeast mitochondrial intermembrane space. Tim9p, Tim10p, and Tim12p mediate the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane and interact structurally and functionally with Tim8p and Tim13p. DDP is most similar to Tim8p. Tim8p exists as a soluble 70-kDa complex with Tim13p and Tim9p, and deletion of Tim8p is synthetically lethal with a conditional mutation in Tim10p. The deafness dystonia syndrome thus is a novel type of mitochondrial disease that probably is caused by a defective mitochondrial protein-import system.
Koehler
C M
CM
Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Leuenberger
D
D
Merchant
S
S
Renold
A
A
Junne
T
T
Schatz
G
G
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D004421:Dystonia / Q000235:genetics*; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013367:Submitochondrial Particles / Q000378:metabolism; D013577:Syndrome
D002352:Carrier Proteins; C101252:DDP2 protein, E coli; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011506:Proteins; D011994:Recombinant Proteins; C118122:TIMM8A protein, human