Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome
| Autor: | Jürgen Seeger, Hanns Lochmüller, Mario Chevrette, Bertold Schrank, Brett A. Kaufman, Hana Antonicka, Florin Sasarman, Jill E. Kolesar, Eric A. Shoubridge, Rita Horvath, Woranontee Weraarpachai |
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| Rok vydání: | 2009 |
| Předmět: |
Genetics
Mitochondrial DNA Mitochondrial translation Activator (genetics) Protein subunit Microfilament Proteins Cytochrome-c Oxidase Deficiency Biology medicine.disease Electron Transport Complex IV Gene product Mutation medicine biology.protein Humans Cytochrome c oxidase Leigh Disease Leigh disease Gene Chromosomes Human Pair 17 Genome-Wide Association Study Microsatellite Repeats |
| Zdroj: | Nature Genetics. 41:833-837 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.390 |
| Popis: | Eric Shoubridge and colleagues report the identification of a mutation in the CCDC44 gene that is causal in a Leigh syndrome pedigree. The CCDC44 gene product, TACO1, is involved in mitochondrial translation and is the first specific mitochondrial translational activator identified in mammals. Defects in mitochondrial translation are among the most common causes of mitochondrial disease1, but the mechanisms that regulate mitochondrial translation remain largely unknown. In the yeast Saccharomyces cerevisiae, all mitochondrial mRNAs require specific translational activators, which recognize sequences in 5′ UTRs and mediate translation2. As mammalian mitochondrial mRNAs do not have significant 5′ UTRs3, alternate mechanisms must exist to promote translation. We identified a specific defect in the synthesis of the mitochondrial DNA (mtDNA)-encoded COX I subunit in a pedigree segregating late-onset Leigh syndrome and cytochrome c oxidase (COX) deficiency. We mapped the defect to chromosome 17q by functional complementation and identified a homozygous single-base-pair insertion in CCDC44, encoding a member of a large family of hypothetical proteins containing a conserved DUF28 domain. CCDC44, renamed TACO1 for translational activator of COX I, shares a notable degree of structural similarity with bacterial homologs4, and our findings suggest that it is one of a family of specific mammalian mitochondrial translational activators. |
| Databáze: | OpenAIRE |
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