ATPase Inhibitory Factor 1—A Novel Marker of Cellular Fitness and Exercise Capacity?

Figures

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  Figure 1. The potential effect of physical activity on mitochondrial membrane integrity and IF1-permeability in two scenarios. Firstly, IF1 in the blood is proportional (left part of the figure) to the IF1 in mitochondria. Secondly, IF1 in the blood is not proportional (right part of the figure) to the IF1 in mitochondria. In the first scenario, non-exercising people with lower exercise capacity are shown in the upper left corner. They need more IF1 to reduce the risk of ATP hydrolysis (and depletion) in mitochondria during occasional physical effort accompanied by hypoxia and acidosis. More IF1 in mitochondria, according to the proportional concept, translates to more IF1 in the blood. In the same scenario, physically active people with better exercise capacity are presented in the bottom left corner. Such individuals do not need a lot of IF1 in mitochondria due to certain other metabolic adaptations protecting against frequent hypoxia/academia bouts during repeated training. Therefore, in the proportional concept, IF1 is either lower or higher in mitochondria and the circulating blood. The second scenario might be explained by not proportional IF1 content in the blood and mitochondria.…

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  Figure 2. Potential modulation of purinergic signaling by IF1. In intravascular and extracellular space, IF1 binds to ecto-F1-ATPase and inhibits its hydrolytic activity, increasing the pool of circulating ATP. This ATP acts with purinergic P2 family receptors, which, in endothelial cells, activate nitric oxide synthase (eNOS) and nitric oxide (NO) production, thus leading to vasodilation. In muscle cells, an increased pool of extracellular ATP could activate purinergic receptors outside the cell membrane, in turn activating Akt and AMPK kinases. When activated, kinases, AMPK and Akt trigger GLUT4 translocation to the cell surface, thus increasing glucose uptake. Due to vasodilation, the blood delivers more glucose and oxygen to the working muscle. Increased glucose uptake sustains proper glucose delivery to the cell during exercise. Both vasodilation and increased glucose uptake contribute to increased exercise capacity/performance.