Mitochondrial threshold for HO release in skeletal muscle of mammals.

The aim of the study was to evaluate the interplay between mitochondrial respiration and HO release during the transition from basal non-phosphorylating to maximal phosphorylating states. We conducted a large scale comparative study of mitochondrial oxygen consumption, HO release and electron leak (% HO/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 HO 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.