An Energy-Saving Distribution of Mitochondria Activation of ATP Production in Skeletal Muscle. A Design That Minimizes Mitochondria Ros Production

Abstract

Exercise produces oxidants from a variety of intracellular sources, including NADPH oxidases (NOX) and mitochondria. Exercise-derived ROS are beneficial, and the amount and location of these ROS are important to avoid muscle damage associated with oxidative stress. We discuss here some of the evidence that involves ROS production associated with skeletal muscle contraction and the potential oxidative stress associated with muscle contraction. We also discuss the potential role of H2O2 produced after NOX activation in the regulation of glucose transport in skeletal muscle. Finally, we propose a model based on evidence for the role of different populations of mitochondria in skeletal muscle in the regulation of ATP production upon exercise. The sub-sarcolemmal population of mitochondria has the enzymatic and metabolic components to establish a high mitochondrial membrane potential when fissioned at rest but lacks the capacity to produce ATP; calcium entry to the mitochondria will further increase the metabolic input. Upon exercise, sub-sarcolemmal mitochondria will fuse to intermyofibrillar mitochondria and will transfer the membrane potential to them. These mitochondria are rich in ATP synthase and will subsequentially produce the ATP needed for muscle contraction in long-term exercise. These events will optimize energy use and minimize mitochondria ROS production.