Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Hanns Lochmuller, Professor Rita Horvath


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

Author(s): Weraarpachai W, Antonicka H, Sasarman F, Seeger J, Schrank B, Kolesar JE, Lochmuller H, Chevrette M, Kaufman BA, Horvath R, Shoubridge EA

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2009

Volume: 41

Issue: 7

Pages: 833-837

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group


DOI: 10.1038/ng.390


Altmetrics provided by Altmetric


Find at Newcastle University icon    Link to this publication