Mitochondrial threshold for H₂O₂ release in skeletal muscle of mammals

The aim of the study was to evaluate the interplay between mitochondrial respiration and H₂O₂ release during the transition from basal non-phosphorylating to maximal phosphorylating states. We conducted a large scale comparative study of mitochondrial oxygen consumption, H₂O₂ release and electron leak (% H₂O₂/O) in skeletal muscle mitochondria isolated from mammal species ranging from 7 g to 500 kg. Mitochondrial fluxes were measured at different steady state rates in presence of pyruvate, malate, and succinate as respiratory substrates. Every species exhibited a burst of H₂O₂ release from skeletal muscle mitochondria at a low rate of oxidative phosphorylation, essentially once the activity of mitochondrial oxidative phosphorylation reached 26% of the maximal respiration. This threshold for ROS generation thus appears as a general characteristic of skeletal muscle mitochondria in mammals. These findings may have implications in situations promoting succinate accumulation within mitochondria, such as ischemia or hypoxia.