Journal of Bioenergetics and Biomembranes

, Volume 42, Issue 3, pp 199–205 | Cite as

The interrelationship between mitochondrial dysfunction and transcriptional dysregulation in Huntington disease

  • Youngnam N. Jin
  • Gail V. W. JohnsonEmail author


Huntington disease (HD) is an inherited neurodegenerative disease caused by an abnormal expansion of the CAG repeat region in the huntingtin (Htt) gene. Although the pathogenic mechanisms by which mutant Htt (mHtt) causes HD have not been fully elucidated, it is becoming increasingly apparent that mHtt can impair mitochondrial function directly, as well as indirectly by dysregulation of transcriptional processes. mHtt causes increased sensitivity to Ca2+-induced decreases in state 3 respiration and mitochondrial permeability transition pore (mPTP) opening concurrent with a reduction in mitochondrial Ca2+ uptake capacity. Treatment of striatal cells expressing mHtt with thapsigargin results in a decrease in mitochondrial Ca2+ uptake and membrane potential and an increase in reactive oxygen species (ROS) production. Transcriptional processes regulated by peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α), which are critical for mitochondrial biogenesis, have been shown to be impaired in HD. In addition, the PPARγ signaling pathway is impaired by mHtt and the activation of this pathway ameliorates many of the mitochondrial deficits, suggesting that PPARγ agonists may represent an important treatment strategy for HD.


Mitochondria Huntingtin PGC-1α/PPARγ Ca2+ Respiration 


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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Departments of Anesthesiology and Pharmacology & PhysiologyUniversity of RochesterRochesterUSA

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