Cited by 262Amyotrophic Lateral Sclerosis ResearchMitochondrial Function and PathologyCoenzyme Q10 studies and effects

Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis

Wiedemann, Falk R, Winkler, Kirstin, Kuznetsov, Andrey V, Bartels, Claudius, Vielhaber, Stefan, Feistner, Helmut, Kunz, Wolfram S·1998·Journal of the Neurological Sciences

Abstract

In skeletal muscle homogenates of 14 patients with sporadic amyotrophic lateral sclerosis, an approximately twofold lower specific activity of NADH:CoQ oxidoreductase in comparison to an age matched control group (n=28) was detected. This finding was confirmed by a detailed analysis of mitochondrial oxidative phosphorylation in skeletal muscle using saponin-permeabilized muscle fibers. (i) A significantly lowered maximal glutamate+malate and pyruvate+malate supported respiration of saponin-permeabilized fibers was detected in the patients group. (ii) Titrations with the specific inhibitor of NADH:CoQ oxidoreductase amytal revealed a higher sensitivity of respiration to this inhibitor indicating an elevated flux control coefficient of this enzyme. (iii) Applying functional imaging of mitochondria using ratios of NAD(P)H and flavoprotein autofluorescence images of saponin-permeabilized fibers we detected the presence of partially respiratory chain inhibited mitochondria on the single fiber level. A secondary defect of mitochondrial function due to the neurogenic changes in muscle seems to be unlikely since no mitochondrial abnormalities were detectable in biopsies of patients with spinal muscular atrophy. These results support the viewpoint that an impairment of mitochondria may be of pathophysiological significance in the etiology of amyotrophic lateral sclerosis.

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Crossref · 10.1016/s0022-510x(98)00008-2

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  • Accumulations of dysmorphic and enlarged mitochondria, many with deficiencies of critical oxidative enzymes, in anterior horn cells, intramuscular nerves, and skeletal muscle are characteristic of sALS.

    “Accumulations of dysmorphic and enlarged mitochondria, many with deficiencies of critical oxidative enzymes, in anterior horn cells, intramuscular nerves, and skeletal muscle are characteristic of sALS [281–285].”

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Authors
Wiedemann, F. R., Winkler, K., Kuznetsov, A. V., Bartels, C., Vielhaber, S., Feistner, H., & Kunz, W. S.
Affiliations
  • Klinikum Magdeburg (DE)
  • University Hospital Magdeburg (DE)
Corresponding author
Kunz, Wolfram S
Venue
Journal of the Neurological Sciences
Publisher
Elsevier BV
Published
1998-03
Volume
156
Issue
1
Pages
65-72
ISSN
0022-510X (ISSN-L)
OpenAlex
W2020074935
Cited by
262
References
27
Citations by year
2026: 9 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 14
FWCI
6.41
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of the Neurological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Keywords
amyotrophic lateral sclerosis, mitochondrial dysfunction, skeletal muscle, oxidative phosphorylation, electron transport inhibition, amytal, flux control coefficients, NAD(P)H autofluorescence, spinal muscular atrophy
MeSH terms
Adult, Aged, Amyotrophic Lateral Sclerosis, Electromyography, Electron Transport, Female, Humans, Male, Microscopy, Fluorescence, Middle Aged, Mitochondria, Muscle, NAD(P)H Dehydrogenase (Quinone), Muscle, Skeletal

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