Mitochondria in the middle: exercise preconditioning protection of striated muscle

Cellular and physiological adaptations to an atmosphere which became enriched in molecular oxygen spurred the development of a layered system of stress protection, including antioxidant and stress response proteins. At physiological levels reactive oxygen and nitrogen species regulate cell signalling as well as intracellular and intercellular communication. Exercise and physical activity confer a variety of stressors on skeletal muscle and the cardiovascular system: mechanical, metabolic, oxidative. Transient increases of stressors during acute bouts of exercise or exercise training stimulate enhancement of cellular stress protection against future insults of oxidative, metabolic and mechanical stressors that could induce injury or disease. This phenomenon has been termed both hormesis and exercise preconditioning (EPC). EPC stimulates transcription factors such as Nrf‐1 and heat shock factor‐1 and up‐regulates gene expression of a cadre of cytosolic (e.g. glutathione peroxidase and heat shock proteins) and mitochondrial adaptive or stress proteins (e.g. manganese superoxide dismutase, mitochondrial KATP channels and peroxisome proliferator activated receptor γ coactivator‐1 (PGC‐1)). Stress response and antioxidant enzyme inducibility with exercise lead to protection against striated muscle damage, oxidative stress and injury. EPC may indeed provide significant clinical protection against ischaemia–reperfusion injury, Type II diabetes and ageing. New molecular mechanisms of protection, such as δ‐opioid receptor regulation and mitophagy, reinforce the notion that mitochondrial adaptations (e.g. heat shock proteins, antioxidant enzymes and sirtuin‐1/PGC‐1 signalling) are central to the protective effects of exercise preconditioning. Mild, non‐exhaustive exercise results in a rise in reactive oxygen species (ROS) that leads to cellular adaptations capable of offering defence against ischemia–reperfusion (I/R) injury in striated muscle fibres. These exercise‐induced cardiac and skeletal muscle adaptations are referred to as exercise preconditioning (EPC). EPC induces ROS production from mitochondria, NADPH oxidase (Nox) and xanthine oxidase (XO). The ROS produced from these oxidant sources leads to increased expression and post‐translational modifications of cytosolic antioxidants and cytosolic HSPs, and enhanced nitric oxide signalling. Mitochondrial adaptations such as increased MnSOD, Trx2, NADP‐specific isocitrate dehydrogenase (ICDH‐NADP), mitochdonrial