Human deafness dystonia syndrome is a mitochondrial disease
Open Access
- 2 March 1999
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 96 (5) , 2141-2146
- https://doi.org/10.1073/pnas.96.5.2141
Abstract
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.Keywords
This publication has 23 references indexed in Scilit:
- The Tim54p–Tim22p Complex Mediates Insertion of Proteins into the Mitochondrial Inner MembraneThe Journal of cell biology, 1997
- PROTEIN IMPORT INTO MITOCHONDRIAAnnual Review of Biochemistry, 1997
- Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22Nature, 1996
- A novel X–linked gene, DDP, shows mutations in families with deafness (DFN–1), dystonia, mental deficiency and blindnessNature Genetics, 1996
- Common Principles of Protein Translocation Across MembranesScience, 1996
- Protein translocation across mitochondrial membranes: What a long, strange trip it isCell, 1995
- trans-Golgi retention of a plasma membrane protein: mutations in the cytoplasmic domain of the asialoglycoprotein receptor subunit H1 result in trans-Golgi retention.The Journal of cell biology, 1995
- Mitochondrial DNA mutations in human degenerative diseases and agingBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.Journal of Medical Genetics, 1995
- New heterologous modules for classical or PCR‐based gene disruptions in Saccharomyces cerevisiaeYeast, 1994