Selective striatal mtDNA depletion in end-stage Huntington's disease R6/2 mice

Exp Neurol. 2015 Apr;266:22-9. doi: 10.1016/j.expneurol.2015.02.004. Epub 2015 Feb 12.


In Huntington's disease (HD) the striatum and cortex seem particularly vulnerable. Mitochondrial dysfunction can also cause neurodegeneration with prominent striatal involvement very similar to HD. We first examined if mitochondrial biogenesis, mitochondrial DNA (mtDNA) transcription, and the implications for mitochondrial respiratory chain (MRC) assembly and function differ between the striatum and cortex compared with the whole brain average in the healthy mouse brain. We then examined the effects of the mutant huntingtin transgene in end-stage R6/2 mice. In wild-type mice, mitochondrial mass (citrate synthase levels, mtDNA copy number) was higher in the striatum than in the cortex or whole brain average. PGC-1α and TFAM mRNA levels were also higher in the striatum than the whole brain average and cortex. mRNA reserve for MRC Complex proteins was higher in the striatum and cortex. In addition, in the cortex a greater part of mitochondrial mass was dedicated to the generation of ATP by oxidative phosphorylation than in the striatum or on average in the brain. In the HD transgenic striatum there was selective mtDNA depletion without evidence that this translated to abnormalities of steady-state MRC function. Our data indicate that in mice the striatum differs from the cortex, or whole brain average, in potentially important aspects of mitochondrial biology. This may contribute to the increased vulnerability of the striatum to insults such as the HD mutation, causing selective striatal mtDNA depletion in end-stage R6/2 mice.

Keywords: Mitochondrial biogenesis; Mitochondrial respiratory chain assembly; PGC-1α; TFAM; mtDNA depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Citrate (si)-Synthase / biosynthesis
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Electron Transport / drug effects
  • Electron Transport / genetics
  • Gene Dosage
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Mice
  • Mutation / genetics
  • Neostriatum / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Transcription, Genetic


  • DNA, Mitochondrial
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Adenosine Triphosphate
  • Citrate (si)-Synthase