Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy
- 7 April 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 13 (588)
- https://doi.org/10.1126/scitranslmed.abb0319
Abstract
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, and despite advances in genetic and pharmacological disease-modifying treatments, its management remains a major challenge. Mitochondrial dysfunction contributes to DMD, yet the mechanisms by which this occurs remain elusive. Our data in experimental models and patients with DMD show that reduced expression of genes involved in mitochondrial autophagy, or mitophagy, contributes to mitochondrial dysfunction. Mitophagy markers were reduced in skeletal muscle and in muscle stem cells (MuSCs) of a mouse model of DMD. Administration of the mitophagy activator urolithin A (UA) rescued mitophagy in DMD worms and mice and in primary myoblasts from patients with DMD, increased skeletal muscle respiratory capacity, and improved MuSCs’ regenerative ability, resulting in the recovery of muscle function and increased survival in DMD mouse models. These data indicate that restoration of mitophagy alleviates symptoms of DMD and suggest that UA may have potential therapeutic applications for muscular dystrophies.Keywords
Funding Information
- École Polytechnique Fédérale de Lausanne
- Commission for Technology and Innovation (15171.1 PFLS-LS)
- Sigrid Juselius Foundation
- École Polytechnique Fédérale de Lausanne (n/a)
- Fondation Marcel Levaillant (n/a)
- Swiss Foundation for Research on Muscle Diseases (n/a)
- funding
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