M.I.2 - Exercise and mitochondrial function in health and disease

Abstract

The capacity to sustain exercise for more than a few minutes depends upon the ability of the skeletal muscle to generate ATP via oxidative phosphorylation to power muscle contractions. Muscle aerobic energy production in turn depends upon the delivery of oxygen by the circulation and upon the quantity and integrity of muscle mitochondria – particularly the mitochondrial respiratory chain – where oxygen is extracted and metabolized in the process of oxidative phosphorylation. The range of aerobic exercise capacity in healthy humans depends to a great extent upon habitual patterns of exercise that determine both peak capacity for oxygen delivery and peak levels of mitochondrial oxidative phosphorylation. Regular aerobic exercise increases exercise capacity and reduces exercise effort during submaximal exercise; a habitually sedentary lifestyle does the opposite. Exercise intolerance that may be profound is typical of mitochondrial myopathies that limit the rate of oxidative phosphorylation and restrict the extraction of oxygen from blood; but evidence from several studies supports the view that regular exercise can ameliorate the mitochondrial defect whereas habitual inactivity worsens already limited peak levels of oxidative phosphorylation. We will review current recommendations for the use of exercise training as a therapy in mitochondrial myopathy while highlighting the remaining gaps in our understanding of this approach to the management of patients with mitochondrial myopathy.