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D03 Mitochondrial Biogenesis, And Respiratory Chain Assembly And Function, In Skeletal Muscle Of The R6/2 Mouse Model And Human Huntington’s Disease
  1. T Hering1,
  2. K Kojer1,
  3. N Birth1,
  4. T Lenk1,
  5. JA Parker2,
  6. S Haider2,
  7. SJ Tabrizi2,
  8. J Taanman3,
  9. M Orth1
  1. 1Department of Neurology, Ulm University, Ulm, Germany
  2. 2Department of Neurodegenerative Disease UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery Queen Square London, London, UK
  3. 3Department of Clinical Neurosciences, University College London, London, UK


Background Huntington’s disease (HD) primarily affects the brain. However, Huntingtin (HTT) is expressed in peripheral tissues as well. In skeletal muscle, like brain a post-mitotic tissue, multiple mitochondrial DNA deletions as well as variable deficits in complex I of the mitochondrial respiratory chain (MRC), abnormal calcium handling, and reduced expression of PGC-1α have been described. In addition, myoblast cell cultures from pre-manifest and manifest HD subjects showed impaired cell differentiation and HTT inclusions similar to those in brain.

Aims To assess mitochondrial biogenesis, MRC assembly and MRC function in R6/2 and human skeletal muscle.

Methods/techniques We used quadriceps muscle tissue from 12-week old R6/2 HD transgenic mice, and near to motor onset pre-manifest HD (n = 20), early onset HD patients (n = 20) and sex and age matched healthy controls (n = 20), as part of the Multi-Tissue Molecular signatures in HD project (MTM-HD).

Results We report on the expression of PGC1α and one of its downstream targets, the mitochondrial transcription factor TFAM. Since TFAM regulates mitochondrial DNA transcription we determined the amount of mitochondrial DNA copies. Mitochondrial DNA encodes subunits of the respiratory chain complexes I, III and IV. We therefore assessed the assembly and the levels of the MRC complexes and measured their activities.

  • skeletal muscle
  • mtDNA copy number
  • MRC holo-enzyme

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