Mitochondrial function in saponin-permeabilized muscle fibres can be studied by high-resolution respirometry, laser-excited fluorescence spectroscopy and fluorescence microscopy. We applied these techniques to study metabolic effects of changes in the pattern of mitochondrial enzymes in skeletal muscle of patients with chronic progressive external ophthalmoplegia or Kearns-Sayre syndrome harbouring large-scale deletions of mitchondrial DNA (mtDNA). In all patients combined deficiencies of respiratory chain enzymes containing mitochondrially encoded subunits were observed. The citrate synthase-normalized activity ratios of these enzymes decreased linearly with increasing mtDNA heteroplasmy. This indicates the absence of any well-defined mutation thresholds for mitochondrial enzyme activities in the entire skeletal muscle. We applied metabolic control analysis to perform a quantitative estimation of the metabolic influence of the observed enzyme deficiencies. For patients with degrees of mtDNA heteroplasmy below about 60% we observed at almost normal maximal rates of respiration an increase in flux control coefficients of complexes I and IV. Permeabilized skeletal-muscle fibres of patients with higher degrees of mtDNA heteroplasmy and severe enzyme deficiencies exhibited additionally decreased maximal rates of respiration. This finding indicates the presence of a ‘metabolic threshold’ which can be assessed by functional studies of muscle fibres providing the link to the phenotypic expression of the mtDNA mutation in skeletal muscle.
Skip Nav Destination
Article navigation
February 2000
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
February 01 2000
Muscle fibres: applications for the study of the metabolic consequences of enzyme deficiencies in skeletal muscle
S. Vielhaber;
S. Vielhaber
*Department of Neurology, University Magdeburg, Leipziger Str. 44, D 39120 Magdeburg, Germany
Search for other works by this author on:
A. Kudin;
A. Kudin
†Department of Epileptology, University Bonn Medical Center, Sigmund-Freud-Str. 25, D 53105 Bonn, Germany
Search for other works by this author on:
R. Schröder;
R. Schröder
‡Department of Neurology, University Bonn Medical Center, Sigmund-Freud-Str. 25, D 53105 Bonn, Germany
Search for other works by this author on:
C. E. Elger;
C. E. Elger
†Department of Epileptology, University Bonn Medical Center, Sigmund-Freud-Str. 25, D 53105 Bonn, Germany
Search for other works by this author on:
W. S. Kunz
W. S. Kunz
1
†Department of Epileptology, University Bonn Medical Center, Sigmund-Freud-Str. 25, D 53105 Bonn, Germany
1To whom correspondence should be addressed.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 12 1999
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2000 Biochemical Society
2000
Biochem Soc Trans (2000) 28 (2): 159–164.
Article history
Received:
August 12 1999
Citation
S. Vielhaber, A. Kudin, R. Schröder, C. E. Elger, W. S. Kunz; Muscle fibres: applications for the study of the metabolic consequences of enzyme deficiencies in skeletal muscle. Biochem Soc Trans 1 February 2000; 28 (2): 159–164. doi: https://doi.org/10.1042/bst0280159
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.