Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health

Abstract

Physical exercise promotes cardiorespiratory fitness, and is considered the mainstream of non-pharmacological therapies along with lifestyle modification for various chronic diseases, in particular cardiovascular diseases. Physical exercise may positively affect various cardiovascular risk factors including body weight, blood pressure, insulin sensitivity, lipid and glucose metabolism, heart function, endothelial function, and body fat composition. With the ever-rising prevalence of obesity and other types of metabolic diseases, as well as sedentary lifestyle, regular exercise of moderate intensity has been indicated to benefit cardiovascular health and reduce overall disease mortality. Exercise offers a wide cadre of favorable responses in the cardiovascular system such as improved dynamics of the cardiovascular system, reduced prevalence of coronary heart diseases and cardiomyopathies, enhanced cardiac reserve capacity, and autonomic regulation. Ample clinical and experimental evidence has indicated an emerging role for autophagy, a conservative catabolism process to degrade and recycle cellular organelles and nutrients, in exercise training-offered cardiovascular benefits. Regular physical exercise as a unique form of physiological stress is capable of triggering adaptation while autophagy in particular selective autophagy seems to be permissive to such cardiovascular adaptation. Here in this mini-review, we will summarize the role for autophagy in particular mitochondrial selective autophagy namely mitophagy in the benefit versus risk of physical exercise on cardiovascular function.

Mitochondrial Ca2+ regulation in the etiology of heart failure: physiological and pathophysiological implications

“…Ample evidence has suggested that mitochondrial architecture is constantly modified by highly dynamic organelle transformations [ 30 , 122 – 124 ]. Mitochondria undergo continuous fission and fusion to maintain mitochondrial integrity and remove damaged mitochondria [ 125 , 126 ]. Dynamin-related protein 1 (DRP1) is recruited to mitochondria and forms a constricted ring that drives mitochondrial fragmentation.…”

“…Dynamin-related protein 1 (DRP1) is recruited to mitochondria and forms a constricted ring that drives mitochondrial fragmentation. In contrast, mitochondrial fusion is regulated by MFN1, MFN2, and optic atrophy protein 1 (OPA1) [ 125 – 127 ]. MFN1/MFN2 are located on the membrane of two adjacent mitochondria that interact with each other to mediate OMM fusion.…”

“…Interfering with mitochondrial quality control results in the accumulation of dysfunctional mitochondria and, ultimately, cardiac dysfunction [ 26 ]. Mitophagy is an essential process of selective autophagy, which results in the removal of irreversibly damaged mitochondria [ 125 , 126 ]. Emerging evidence supports the protective role of mitophagy in the progression of HF [ 125 , 126 , 133 ].…”

“…Mitophagy is an essential process of selective autophagy, which results in the removal of irreversibly damaged mitochondria [ 125 , 126 ]. Emerging evidence supports the protective role of mitophagy in the progression of HF [ 125 , 126 , 133 ]. Mitophagy is mainly mediated by the PINK1/Parkin pathway.…”

Sex/Gender-Specific Imbalance in CVD: Could Physical Activity Help to Improve Clinical Outcome Targeting CVD Molecular Mechanisms in Women?

“…In particular, in a systematic review and meta-analysis, Lin and colleagues clearly indicated that exercise training improved cardiorespiratory fitness and cardiometabolic biomarkers belonging to different biological pathways, such as lipid/lipoprotein metabolism, glucose intolerance, insulin resistance, and systemic hemostasis/inflammation, thereby highlighting sex as one of the variables that may differentiate the effects and benefits of exercise at the CV level together with age and health status [90]. Other advantages have also been reported, including positive effects on mitochondrial function, re-establishment of vasculature, release of myokines from the skeletal muscle that preserve or augment cardiovascular functions [91], and mitochondrial selective autophagy in the view of the crucial role of mitochondria in maintaining cardiac homeostasis (Figure 3) [92]. It is worth noting that different consideration and attention should be paid to different types of physical activities.…”