Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice

Ann Neurol. 2006 Feb;59(2):407-11. doi: 10.1002/ana.20754.

Abstract

Objective: The aim of the present work was the detection of Mitochondrial dysfunction of Huntington's disease (HD).

Methods: We investigated muscle and muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type mice.

Results: Atrophic fibers, increased fuchsinophilic aggregates, and reduced cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements and Ca2+ accumulation experiments, a decreased stability of HD mitochondria against Ca2+-induced permeability transition was detected. Complex I-dependent respiration of HD mitochondria was more sensitive to inhibition by adding 10 microm Ca2+ than wild-type mitochondria.

Interpretation: Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Huntington Disease / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondria, Muscle / drug effects*
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Oxygen Consumption / drug effects
  • Respiration / drug effects
  • Time Factors
  • Trinucleotide Repeats / genetics

Substances

  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Calcium