title: Aerobic conditioning in patients with mitochondrial myopathies: physiological, biochemical, and genetic effects.
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 (approximately 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.
authors.affiliation: Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, TX 75231, USA.
authors.forename: T
authors.initials: T
authors.lastname: Taivassalo
authors.forename: E A
authors.initials: EA
authors.lastname: Shoubridge
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: N G
authors.initials: NG
authors.lastname: Kennaway
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.forename: D L
authors.initials: DL
authors.lastname: Arnold
authors.forename: R G
authors.initials: RG
authors.lastname: Haller
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D013997:Time Factors