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


CONCLUSIONS
Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy.
Gizatullina
Zemfira Z
ZZ
KeyNeurotek AG, ZENIT Technology Park, Magdeburg, Germany.
Lindenberg
Katrin S
KS
Harjes
Phoebe
P
Chen
Ying
Y
Kosinski
Christoph M
CM
Landwehrmeyer
Bernhard G
BG
Ludolph
Albert C
AC
Striggow
Frank
F
Zierz
Stephan
S
Gellerich
Frank N
FN
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010101:Oxygen Consumption / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013997:Time Factors; D018911:Trinucleotide Repeats / Q000235:genetics
C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D002118:Calcium