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Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p &lt, 0.01). Citrate synthase and mitochondrial respiratory chain complex I&ndash, IV activities were increased by 51% and 46&ndash, 61%, respectively, in the trained leg (p &lt, 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I&ndash, IV activities by 29&ndash, 36% (p &lt, 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.

Introduction: In this study we investigated the effect of 12 weeks of cycle ergometer training in patients with spinal muscular atrophy type III (SMA III), a hereditary motor neuron disease with progressive muscle weakness and atrophy. Methods: Six SMA III patients and 9 healthy subjects completed a 12-week training program, performing 42 30-minute sessions exercising at 65-70% of maximal oxygen uptake (VO2max). VO2max, muscle strength, functional tests, and self-reported activities of daily living were assessed before and after the training. Results: Training induced a 27 63% increase in VO2max (17 6 2t o 2162 ml/kg/min, P < 0.001) in patients. However, fatigue was a major complaint and caused 1 patient to drop out, increased the need for sleep in 3 patients, and led to train- ing modifications in 2 patients. Conclusions: Cycle exercise improves VO2max in SMA III without causing muscle damage, but it also induces significant fatigue. This warrants study into alternative training methods to improve exercise capacity in SMA III patients. Muscle Nerve 000:000-000, 2014 Spinal muscular atrophy (SMA) is a motor neu- ron disease caused by autosomal recessively inher- ited mutations in the survival motor neuron gene (SMN1). Mutations in SMN1 cause a loss of ante- rior horn cells in the spinal cord and lead to denervation of skeletal muscles and progressive muscle weakness and atrophy. SMA type III (SMA III) is the mildest subtype of SMA. It is defined by onset of symptoms after age 18 months with patients retaining the ability to walk. 1 No effective treatment is available for SMA. We have previously shown that patients with muscular dystrophies improve oxidative capacity (VO2max) and muscle strength by aerobic conditioning. 2-4 Patients with SMA III share many clinical features with these conditions, although the mechanism of muscle weakness is different. In this study, we investigated how patients with SMA III respond to aerobic training. METHODS