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Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

Ehinger, Johannes LU orcid ; Morota, Saori LU ; Hansson, Magnus LU orcid ; Paul-Visse, Gesine LU and Elmer, Eskil LU orcid (2015) In Journal of Neurology 262(6). p.1493-1503
Abstract
Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and... (More)
Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease. (Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurology
volume
262
issue
6
pages
1493 - 1503
publisher
Springer
external identifiers
  • pmid:25893255
  • wos:000356296600011
  • scopus:84931010356
  • pmid:25893255
ISSN
1432-1459
DOI
10.1007/s00415-015-7737-0
project
EU FP Horizon 2020 COST Action CA15203 MITOEAGLE
Investigation of mitochondrial function in blood cells from patients with chronic neurodegenerative or muscular disorders
language
English
LU publication?
yes
id
26fc57c3-bebb-4ed5-a4d4-11b8a8cbd48f (old id 5341230)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25893255?dopt=Abstract
date added to LUP
2016-04-01 10:08:54
date last changed
2024-01-21 06:30:23
@article{26fc57c3-bebb-4ed5-a4d4-11b8a8cbd48f,
  abstract     = {{Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease.}},
  author       = {{Ehinger, Johannes and Morota, Saori and Hansson, Magnus and Paul-Visse, Gesine and Elmer, Eskil}},
  issn         = {{1432-1459}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1493--1503}},
  publisher    = {{Springer}},
  series       = {{Journal of Neurology}},
  title        = {{Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.}},
  url          = {{http://dx.doi.org/10.1007/s00415-015-7737-0}},
  doi          = {{10.1007/s00415-015-7737-0}},
  volume       = {{262}},
  year         = {{2015}},
}