Utrophin influences mitochondrial pathology and oxidative stress in dystrophic muscle

Using transmission electron microscopy, we show that high levels of utrophin ameliorate the aberrant structure and localisation of mitochondria in mdx mice whereas absence of utrophin worsened these features in dko mice

Tahnee L. Kennedy; Lee Moir; Sarah Hemming; Ben Edwards; Sarah Squire; Kay Davies; Simon Guiraud

2017

Scholarcy highlights

  • Duchenne muscular dystrophy is a lethal X-linked muscle wasting disorder caused by the absence of dystrophin, a large cytoskeletal muscle protein
  • Loss of dystrophin and utrophin from the sarcolemma leads to membrane rupture Prior to the investigation of mitochondrial pathology, we first confirmed the phenotypes of the mouse strains used
  • Elevated utrophin in dystrophic muscle reverted markers of protein carbonylation and oxidative stress to wildtype levels. These changes were observed independently from a shift in oxidative phenotype. These findings show that utrophin overexpression benefits mitochondria in dystrophic muscle and attenuates the downstream pathology associated with aberrant mitochondrial function
  • Here, we show that utrophin over-expression in dystrophic muscle improves mitochondrial structure/localisation and reduces oxidative stress and that these benefits are potentially due to improved membrane integrity
  • Our results highlight the effectiveness of utrophin in alleviating mitochondrial pathology resulting from dystrophin deficiency
  • We demonstrate the antioxidant effect of utrophin modulation, further elucidating its molecular impact on dystrophic muscle and relevance in multi-faceted treatment approaches for DMD patients

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