Coenzyme Q improves mitochondrial and muscle dysfunction caused by CUG expanded repeats in Caenorhabditis elegans.

Expansion of nucleotide repeat sequences is associated with more than 40 human neuromuscular disorders. The different pathogenic mechanisms associated with the expression of nucleotide repeats are not well understood. We use a Caenorhabditis elegans model that expresses expanded CUG repeats only in cells of the body wall muscle and recapitulate muscle dysfunction and impaired organismal motility to identify the basis by which expression of RNA repeats is toxic to muscle function. Here, we performed 2 consecutive RNA interference screens and uncovered coenzyme Q metabolism and mitochondrial dysfunction as critical genetic modifiers of the motility phenotype. Furthermore, coenzyme Q supplementation reduced the toxic phenotypes, ameliorating the motility impairment and mitochondrial phenotypes. Together our data show how the expression of expanded RNA repeats can be toxic to mitochondrial homeostasis.