Cardiac damage is a major contributor to the morbidity and mortality particularly associated with coronary artery disease. Moreover, it is also related to some metabolic diseases such as diabetes and to some side effects of drug treatments. Regular exercise has been confirmed as a pragmatic countermeasure to protect against cardiac injury. Specifically, life-long physical activity and endurance exercise training have been proven to provide cardioprotection against cardiac insults in both young and old animals. It is suggested that the beneficial effects resulting from increased physical activity levels occur at different levels of cellular organization, being mitochondria preferential target organelles. At present, it remains unclear what are the protective mechanisms that are essential for exercise-induced cardioprotection. Proposed mechanisms to explain the cardioprotective effects of exercise are mediated, at least partially, by redox changes and include the up-regulation of mitochondrial chaperones, improved antioxidant capacity, and/or elevation of other protective molecules against cellular death. It is possible that under some conditions, exercise also diminishes the increased susceptibility of cardiac mitochondria to undergo permeability transition pore opening through the modulation of pore components or sensitizers.
The role of physical exercise against the impairment of heart mitochondrial function that accompany ageing, diabetes, administration of the anti-cancer agent Doxorubicin and ischemia-reperfusion is analysed in the present review, which provides biochemical, functional and morphological data illustrating the cross tolerance effect of exercise in these conditions predisposing to cardiac “mitotoxicity”. However, further work should be addressed in order to clarify the precise regulatory mechanisms by which physical exercise augments heart mitochondrial tolerance against many conditions predisposing to dysfunction.