Work

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

Year: 2024

Type: article

Abstract: 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.

Source: Genetics

DOI: 10.1093/genetics/iyae208

Authors: Joana Teixeira, Anu-Mari Harju, Alaa Othman, Ove Eriksson, Brendan J Battersby, Susana M D A Garcia

Institutions: University of Helsinki, HiLIFE – Elämäntieteiden Instituutti, ETH Zurich, Institute for Molecular Systems Biology

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,611