Resistance training in patients with single, large-scale deletions of mitochondrial DNA.
Dramatic tissue variation in mitochondrial heteroplasmy has been found to exist in patients with sporadic mitochondrial DNA (mtDNA) mutations. Despite high abundance in mature skeletal muscle, levels of the causative mutation are low or undetectable in satellite cells. The activation of these typically quiescent mitotic cells and subsequent shifting of wild-type mtDNA templates to mature muscle have been proposed as a means of restoring a more normal mitochondrial genotype and function in these patients. Because resistance exercise is known to serve as a stimulus for satellite cell induction within active skeletal muscle, this study sought to assess the therapeutic potential of resistance training in eight patients with single, large-scale mtDNA deletions by assessing: physiological determinants of peak muscle strength and oxidative capacity and muscle biopsy-derived measures of damage, mtDNA mutation load, level of oxidative impairment and satellite cell numbers. Our results show that 12 weeks of progressive overload leg resistance training led to: (i) increased muscle strength; (ii) myofibre damage and regeneration; (iii) increased proportion of neural cell adhesion molecule (NCAM)-positive satellite cells; (iv) improved muscle oxidative capacity. Taken together, we believe these findings support the hypothesis of resistance exercise-induced mitochondrial gene-shifting in muscle containing satellite cells which have low or absent levels of deleted mtDNA. Further investigation is warranted to refine parameters of the exercise training protocol in order to maximize the training effect on mitochondrial genotype and treatment potential for patients with selected, sporadic mutations of mtDNA in skeletal muscle.
Murphy
Julie L
JL
Mitochondrial Research Group, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.
Blakely
Emma L
EL
Schaefer
Andrew M
AM
He
Langping
L
Wyrick
Phil
P
Haller
Ronald G
RG
Taylor
Robert W
RW
Turnbull
Douglass M
DM
Taivassalo
Tanja
T
D000328:Adult; D001706:Biopsy; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D017079:Exercise Tolerance; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D010349:Patient Compliance; D011788:Quality of Life; D012038:Regeneration; D055070:Resistance Training / Q000379:methods*; D016896:Treatment Outcome
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV