Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects
Article first published online: 27 APR 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 50, Issue 2, pages 133–141, August 2001
How to Cite
Taivassalo, T., Shoubridge, E. A., Chen, J., Kennaway, N. G., DiMauro, S., Arnold, D. L. and Haller, R. G. (2001), Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects. Ann Neurol., 50: 133–141. doi: 10.1002/ana.1050
- Issue published online: 30 JUL 2001
- Article first published online: 27 APR 2001
- Manuscript Accepted: 22 FEB 2001
- Manuscript Revised: 21 FEB 2001
- Manuscript Received: 10 OCT 2000
- Muscular Dystrophy Association (RGH)
- VA Merit Review (RGH)
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.