Original Article

Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects

  1. Tanja Taivassalo PhD1,4,
  2. Eric A. Shoubridge PhD3,4,
  3. Jacqueline Chen M Eng2,4,
  4. Nancy G. Kennaway DPhil5,
  5. Salvatore DiMauro MD6,
  6. Douglas L. Arnold MD2,4,
  7. Ronald G. Haller MD1,7,*

Article first published online: 27 APR 2001

DOI: 10.1002/ana.1050

Issue

Annals of Neurology

Annals of Neurology

Volume 50, Issue 2, pages 133–141, August 2001

Additional Information

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

Author Information

  1. 1

    Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, TX

  2. 2

    Magnetic Resonance Spectroscopy Unit, McGill University, Montreal, Canada

  3. 3

    Department of Human Genetics, McGill University, Montreal, Canada

  4. 4

    Neurology and Neurosurgery, McGill University, Montreal, Canada

  5. 5

    Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, OR

  6. 6

    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY

  7. 7

    VA Medical Center and University of Texas Southwestern Medical Center, Dallas, TX

*Institute of Exercise and Environmental Medicine, Presbyterian Hospital, 7232 Greenville Ave, Dallas, TX 75231

Publication History

  1. Issue published online: 30 JUL 2001
  2. Article first published online: 27 APR 2001
  3. Manuscript Accepted: 22 FEB 2001
  4. Manuscript Revised: 21 FEB 2001
  5. Manuscript Received: 10 OCT 2000

Funded by

  • Muscular Dystrophy Association (RGH)
  • VA Merit Review (RGH)

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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.

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