Letter abstract


Nature Genetics 41, 833 - 837 (2009)
Published online: 7 June 2009 | doi:10.1038/ng.390

Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome

Woranontee Weraarpachai1,2,8, Hana Antonicka2,8, Florin Sasarman1,2, Jürgen Seeger3, Bertold Schrank4, Jill E Kolesar2, Hanns Lochmüller5,7, Mario Chevrette6, Brett A Kaufman2, Rita Horvath5,7 & Eric A Shoubridge1,2

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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.

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  1. Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  2. Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
  3. Department of Pediatrics, Deutsche Klinik für Diagnostik GmbH, Wiesbaden, Germany.
  4. Department of Neurology, Deutsche Klinik für Diagnostik GmbH, Wiesbaden, Germany.
  5. Friedrich-Baur Institute, Ludwig-Maximilians-University, Munich, Germany.
  6. Department of Surgery, Urology Division, McGill University and The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
  7. Present addresses: Institute of Human Genetics, Newcastle University, Newcastle, UK (H.L.) and Mitochondrial Research Group, Newcastle University, Newcastle, UK (R.H.).
  8. These authors contributed equally to this work.

Correspondence to: Eric A Shoubridge1,2 e-mail: eric@ericpc.mni.mcgill.ca



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