Submitted on January 17, 2007
Accepted on May 28, 2007
The effect of training on the expression of mitochondrial biogenesis- and apoptosis- related proteins in skeletal muscle of patients with mtDNA defects
Peter J Adhihetty1, Tanja Taivassalo2, Ronald G Haller3, Donald R Walkinshaw4, and David A Hood5*
1 Biology, York University, Toronto, Canada
2 Kinesiology and Physical Education, McGill University, Montreal, Canada
3 Institute for Exercise and Environmental Medicine, University of Texas Southwestern, Dallas, Texas, United States
4 Kinesiology and Health Science, York University, Toronto, Canada
5 Kinesiology and Health Science, York University, Toronto, Canada; Biology, York University, Toronto, Canada
* To whom correspondence should be addressed. E-mail: dhood{at}yorku.ca.
Mitochondrial myopathy patients (MMPs) have impaired oxidative phosphorylation and exercise intolerance. Training of MMPs improves exercise tolerance, but also increases mutational load. To assess the regulation of mitochondrial content in MMPs, we measured proteins involved in: 1) biogenesis, 2) oxidative stress, and 3) apoptosis in MMPs and healthy controls (HCs) both pre- and post-endurance training. Prior to training, MMPs had a greater mitochondrial content, along with a 1.4-fold (p<0.05) higher expression of PGC-1
. The DNA repair enzyme OGG-1, the anti-oxidant MnSOD, and the apoptotic proteins AIF and Bcl-2 were higher in MMPs compared to HCs. Aconitase, an enzyme sensitive to oxidative stress, was 52% lower (p<0.05) in MMPs when calculated based on mitochondrial volume, and oxidative stress-induced protein modifications tended to be higher in MMPs compared to HCs. Endurance training (ET) induced increases in mitochondria in both HC subjects and MMPs, but there was no effect of training on Tfam or PGC-1. In MMPs, training induced a reduction of OGG-1, an increase in MnSOD, and a reduction in aconitase activity. Thus, prior to training, MMPs exhibited an adaptive response of nuclear proteins indicative of a compensatory increase in mitochondrial content. Following training, several parallel adaptations occurred in MMPs and HCs which may contribute to previously observed functional improvements in MMPs. However, our results indicate that muscle from MMPs may be exposed to greater levels of oxidative stress during training. Further investigation is required to evaluate the long-term benefits of endurance training as a therapeutic intervention for mitochondrial myopathy patients.
