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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/E672    most recent 00043.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Adhihetty, P. J. Articles by Hood, D. A. Search for Related Content PubMed PubMed Citation Articles by Adhihetty, P. J. Articles by Hood, D. A.

The effect of training on the expression of mitochondrial biogenesis- and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects

¹School of Kinesiology and Health Science, and ²Department of Biology, York University, Toronto, Ontario, Canada; ³Institute for Exercise and Environmental Medicine, Utah Southwestern Medical Center, Dallas, Texas; and ⁴Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada

Submitted 17 January 2007 ; accepted in final form 28 May 2007

Mitochondrial myopathy patients (MMPs) have impaired oxidative phosphorylation and exercise intolerance. Endurance 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 before and after endurance training. Before training, MMPs had a greater mitochondrial content, along with a 1.4-fold (P < 0.05) higher expression of the biogenesis regulator peroxisome proliferator-activated receptor- coactivator-1 (PGC-1). The DNA repair enzyme 8-oxoguanine DNA glycolase-1 (OGG-1), the antioxidant manganese superoxide dismutase (MnSOD), and the apoptotic proteins AIF and Bcl-2 were higher in MMPs compared with HCs. Aconitase, an enzyme sensitive to oxidative stress, was 52% lower (P < 0.05) in MMPs when calculated based on an estimate of mitochondrial volume and oxidative stress-induced protein modifications tended to be higher in MMPs compared with HCs. Endurance training (ET) induced increases in mitochondrial content in both HC subjects and MMPs, but there was no effect of training on the regulatory proteins Tfam or PGC-1. In MMPs, training induced a selective reduction of OGG-1, an increase in MnSOD, and a reduction in aconitase activity. Thus, before 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 of exercise in MMPs. However, our results indicate that muscle from MMPs may be exposed to greater levels of oxidative stress during the course of training. Further investigation is required to evaluate the long-term benefits of endurance training as a therapeutic intervention for mitochondrial myopathy patients.

phase 2 enzymes; diabetes; oxidative stress; pancreatic -cells

This article has been cited by other articles:

				T. Wenz, F. Diaz, D. Hernandez, and C. T. Moraes Endurance exercise is protective for mice with mitochondrial myopathy J Appl Physiol, May 1, 2009; 106(5): 1712 - 1719. [Abstract] [Full Text] [PDF]