Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects
- 30 July 2001
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 50 (2), 133-141
- https://doi.org/10.1002/ana.1050
Abstract
Aerobic training has been shown to increase work and oxidative capacity in patients with mitochondrial myopathies, but the mechanisms underlying improvement are not known. We evaluated physiological (cycle exercise, 31P‐MRS), biochemical (enzyme levels), and genetic (proportion of mutant/wild‐type genomes) responses to 14 weeks of bicycle exercise training in 10 patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. Training increased peak work and oxidative capacities (20–30%), systemic arteriovenous O2 difference (20%), and 31P‐MRS indices of metabolic recovery (35%), consistent with enhanced muscle oxidative phosphorylation. Mitochondrial volume in vastus lateralis biopsies increased significantly (50%) and increases in deficient respiratory chain enzymes were found in patients with Complex I (36%) and Complex IV (25%) defects, whereas decreases occurred in 2 patients with Complex III defects (‐20%). These results suggest that the cellular basis of improved oxygen utilization is related to training‐induced mitochondrial proliferation likely resulting in increased levels of functional, wild‐type mtDNA. However, genetic analysis indicated the proportion of wild‐type mtDNA was unchanged (3/9) or fell (6/9), suggesting a trend toward preferential proliferation of mutant genomes. The long‐term implications of training‐induced increases in mutant relative to wild‐type mtDNA, despite positive physiological and biochemical findings, need to be assessed before aerobic training can be proposed as a general treatment option.Keywords
This publication has 29 references indexed in Scilit:
- Exercise Intolerance Due to Mutations in the CytochromebGene of Mitochondrial DNANew England Journal of Medicine, 1999
- Abnormal oxidative metabolism in exercise in exercise intolerance of undetermined originNeuromuscular Disorders, 1997
- Mitochondrial genetics and human diseaseBioEssays, 1996
- Mitochondrial DNA depletion: Prevalence in a pediatric population referred for neurologic evaluationPediatric Neurology, 1996
- Mitochondrial DNA (mtDNA) diseases: correlation of genotype to phenotypeBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1995
- Molecular analysis of the muscle pathology associated with mitochondrial DNA deletionsNature Genetics, 1992
- Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.JCI Insight, 1991
- Deletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial diseaseCell, 1990
- Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency.JCI Insight, 1989
- Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic NeuropathyScience, 1988