Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Jorge M A Oliveira (Author) FFUP; Mika B Jekabsons (Author) Other; Sylvia Chen (Author) Other; Amy Lin (Author) Other; Cristina C Rego (Author) Other; Jorge Goncalves (Author) FFUP; Lisa M Ellerby (Author) Other; David G Nicholls (Author) Other

Journal

Title: Journal of Neurochemistry

Vol. 101

Pages: 241-249

ISSN: 0022-3042

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 88 Citations

Scopus - 108 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-AZ1

DOI: 10.1111/j.1471-4159.2006.04361.x

Abstract (EN): Mitochondrial dysfunction is believed to participate in Huntington's disease (HD) pathogenesis. Here we compare the bioenergetic behavior of forebrain mitochondria isolated from different transgenic HD mice (R6/2, YAC128 and Hdh150 knock-in) and wild-type littermates with the first determination of in situ respiratory parameters in intact HD striatal neurons. We assess the Ca2+-loading capacity of isolated mitochondria by steady Ca2+-infusion. Mitochondria from R6/2 mice (12-13 weeks) and 12 months YAC128, but not homozygous or heterozygous Hdh150 knock-in mice (15-17 weeks), exhibit increased Ca2+-loading capacity when compared with respective wild-type littermates. In situ mitochondria in intact striatal neurons show high respiratory control. Moreover, moderate expression of full-length mutant huntingtin (in Hdh150 knock-in heterozygotes) does not significantly impair mitochondrial respiration in unstimulated neurons. However, when challenged with energy-demanding stimuli (NMDA-receptor activation in pyruvate-based media to accentuate the mitochondria role in Ca2+-handling), Hdh150 neurons are more vulnerable to Ca2+-deregulation than neurons from their wild-type littermates. These results stress the importance of assessing HD mitochondrial function in the cellular context.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9