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Mitochondrial Respiratory Function in Peripheral Blood Cells from Huntington's Disease Patients

EHINGER, JOHANNES LU ; Morota, Saori LU ; Hansson, Magnus LU ; Paul-Visse, Gesine LU and Elmer, Eskil LU (2016) In Movement Disorders Clinical Practice
Abstract
Background

Patients with Huntington's disease display symptoms from both the central nervous system and peripheral tissues. Mitochondrial dysfunction has been implicated as part of the pathogenesis of the disease and has been reported in brain tissue and extracerebral tissues, such as muscle and blood cells, but the results are inconsistent. Therefore, the authors performed a refined evaluation of mitochondrial function in 2 types of peripheral blood cells from 14 patients with Huntington's disease and 21 control subjects. Several hypotheses were predefined, including impaired mitochondrial complex II function (primary), complex I function (secondary), and maximum oxidative phosphorylation capacity (secondary) in patient... (More)
Background

Patients with Huntington's disease display symptoms from both the central nervous system and peripheral tissues. Mitochondrial dysfunction has been implicated as part of the pathogenesis of the disease and has been reported in brain tissue and extracerebral tissues, such as muscle and blood cells, but the results are inconsistent. Therefore, the authors performed a refined evaluation of mitochondrial function in 2 types of peripheral blood cells from 14 patients with Huntington's disease and 21 control subjects. Several hypotheses were predefined, including impaired mitochondrial complex II function (primary), complex I function (secondary), and maximum oxidative phosphorylation capacity (secondary) in patient cells.

Methods

High-resolution respirometry was applied to viable platelets and mononuclear cells. Data were normalized to cell counts, citrate synthase activity, and mitochondrial DNA copy numbers.

Results

Normalized to citrate synthase activity, platelets from patients with Huntington's disease displayed respiratory dysfunction linked to complex I, complex II, and lower maximum oxidative phosphorylation capacity. No difference was seen in mononuclear cells or when platelet data were normalized to cell counts or mitochondrial DNA. The ratio of complex I respiration through maximum oxidative phosphorylation was significantly decreased in patients compared with controls. The corresponding ratio for complex II was unaffected.

Conclusions

The data indicate decreased function of mitochondrial complex I in peripheral blood cells from patients with Huntington's disease, although this could not be uniformly confirmed. The results do not confirm a systemic complex II dysfunction and do not currently support the use of mitochondrial function in blood cells as a biomarker for the disease. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Huntington's disease, mitochondria, blood cells, respirometry, oxygen consumption
in
Movement Disorders Clinical Practice
publisher
John Wiley & Sons
ISSN
2330-1619
DOI
10.1002/mdc3.12308
language
English
LU publication?
yes
id
f6920e95-a80c-4605-ac94-f62ac087529d
date added to LUP
2016-09-26 14:32:47
date last changed
2016-09-27 12:37:47
@misc{f6920e95-a80c-4605-ac94-f62ac087529d,
  abstract     = {Background<br/><br/>Patients with Huntington's disease display symptoms from both the central nervous system and peripheral tissues. Mitochondrial dysfunction has been implicated as part of the pathogenesis of the disease and has been reported in brain tissue and extracerebral tissues, such as muscle and blood cells, but the results are inconsistent. Therefore, the authors performed a refined evaluation of mitochondrial function in 2 types of peripheral blood cells from 14 patients with Huntington's disease and 21 control subjects. Several hypotheses were predefined, including impaired mitochondrial complex II function (primary), complex I function (secondary), and maximum oxidative phosphorylation capacity (secondary) in patient cells.<br/><br/>Methods<br/><br/>High-resolution respirometry was applied to viable platelets and mononuclear cells. Data were normalized to cell counts, citrate synthase activity, and mitochondrial DNA copy numbers.<br/><br/>Results<br/><br/>Normalized to citrate synthase activity, platelets from patients with Huntington's disease displayed respiratory dysfunction linked to complex I, complex II, and lower maximum oxidative phosphorylation capacity. No difference was seen in mononuclear cells or when platelet data were normalized to cell counts or mitochondrial DNA. The ratio of complex I respiration through maximum oxidative phosphorylation was significantly decreased in patients compared with controls. The corresponding ratio for complex II was unaffected.<br/><br/>Conclusions<br/><br/>The data indicate decreased function of mitochondrial complex I in peripheral blood cells from patients with Huntington's disease, although this could not be uniformly confirmed. The results do not confirm a systemic complex II dysfunction and do not currently support the use of mitochondrial function in blood cells as a biomarker for the disease.},
  author       = {EHINGER, JOHANNES and Morota, Saori and Hansson, Magnus and Paul-Visse, Gesine and Elmer, Eskil},
  issn         = {2330-1619},
  keyword      = {Huntington's disease,mitochondria,blood cells,respirometry,oxygen consumption},
  language     = {eng},
  month        = {02},
  publisher    = {ARRAY(0x91bb1a0)},
  series       = {Movement Disorders Clinical Practice},
  title        = {Mitochondrial Respiratory Function in Peripheral Blood Cells from Huntington's Disease Patients},
  url          = {http://dx.doi.org/10.1002/mdc3.12308},
  year         = {2016},
}