C-15L Free Communication/Poster Cellular/Molecular Physiology of Muscle
Mitochondrial myopathy patients possessing mutations in mitochondrial DNA (mtDNA) exhibit a low exercise tolerance despite the presence of a 1.5-fold greater citrate synthase activity, indicative of mitochondrial volume. Endurance training in these patients can lead to further increases in citrate synthase, and improvements in oxidative and work capacities (Ann. Neurol. 50:133, 2001). The molecular mechanisms underlying these adaptations remain unknown.
To assess the expression of selected nuclear-encoded mitochondrial proteins in mitochondrial myopathy patients (MMP) following endurance training.
Eight MMP were trained 3–4 times/wk for 14 weeks at 70–80% max HR. The response was compared to that of healthy control subjects (C). The patients had mtDNA defects that included: 1) large-scale and multiple deletions, 2) point mutations of tRNA, and 3) point mutations in protein coding genes. The proteins measured were chosen as indices of mtDNA transcription (Tfam), protein import (mtHsp70, Tom20), apoptosis (AIF, Bcl-2) and organelle biogenesis (cytochrome c).
Cytochrome c increased by 2.6-fold with training in C, and by 1.8-fold in MMP, similar to the change observed with citrate synthase. MtHSP70 increased by 1.4-fold in C, but 1.6-fold in MMP. While C displayed training-induced increases in Tfam (1.2-fold), Tom20 (1.5-fold), Bcl-2 (1.2-fold) and AIF (1.4-fold), the response of these proteins to training in MMP was attenuated.
The expression of some nuclear genes encoding mitochondrial proteins, which normally respond to training, does not occur in patients with a diversity of mtDNA defects. This suggests that training induces changes in mitochondrial composition which favour an increase in oxidative phosphorylation, but that an altered mitochondrial-to-nuclear signaling mechanism exists in mtDNA-based mitochondrial disease. Supported by CIHR.