Oxidative metabolism and Ca2+ handling in striatal mitochondria from YAC128 mice, a model of Huntington's disease

James Hamilton, Tatiana Brustovetsky, Nickolay Brustovetsky

Research output: Contribution to journalArticle

7 Scopus citations


The mechanisms implicated in the pathology of Huntington's disease (HD) remain not completely understood, although dysfunction of mitochondrial oxidative metabolism and Ca2+ handling have been suggested as contributing factors. However, in our previous studies with mitochondria isolated from the whole brains of HD mice, we found no evidence for defects in mitochondrial respiration and Ca2+ handling. In the present study, we used the YAC128 mouse model of HD to evaluate the effect of mHtt on respiratory activity and Ca2+ uptake capacity of mitochondria isolated from the striatum, the most vulnerable brain region in HD. Isolated, Percoll-gradient purified striatal mitochondria from YAC128 mice were free of cytosolic and ER contaminations, but retained attached mHtt. Both nonsynaptic and synaptic striatal mitochondria isolated from early symptomatic 2-month-old YAC128 mice had similar respiratory rates and Ca2+ uptake capacities compared with mitochondria from wild-type FVB/NJ mice. Consistent with the lack of difference in mitochondrial respiration, we found that the expression of several nuclear-encoded proteins in striatal mitochondria was similar between wild-type and YAC128 mice. Taken together, our data demonstrate that mHtt does not alter respiration and Ca2+ uptake capacity in striatal mitochondria isolated from YAC128 mice, suggesting that respiratory defect and Ca2+ uptake deficiency most likely do not contribute to striatal pathology associated with HD.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalNeurochemistry International
StatePublished - Oct 2017


  • Calcium
  • Huntington's disease
  • Mitochondria
  • Respiration
  • Striatum
  • YAC128

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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