Wiedemann 1998 J Neurol Sci

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156:65-72.

» PMID: 9559989

Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) J Neurol Sci

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.

Keywords: Amyotrophic lateral sclerosis, Mitochondria, Oxidative phosphorylation, NADH:CoQ oxidoreductase

Cited by

Gnaiger 2020 BEC MitoPathways


Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2:112 pp. doi:10.26124/bec:2020-0002


Labels: MiParea: Respiration, mt-Medicine, Patients  Pathology: Inherited 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: TCA cycle and matrix dehydrogenases  Regulation: Substrate 


HRR: Oxygraph-2k 

BEC 2020.2