Threshold effect in the H2O2 production of skeletal muscle mitochondria during fasting and refeeding

Abstract

Under nutritional deprivation, the energetic benefits of reducing mitochondrial metabolism are often associated with enhanced harmful pro-oxidant effects and a subsequent long-term negative impact on cellular integrity. However, the flexibility of mitochondrial functioning under stress has rarely been explored during the transition from basal non-phosphorylating to maximal phosphorylating oxygen consumption. Here, we experimentally tested whether ducklings (Cairina moschata) fasted for 6 days and thereafter refed for 3 days, exhibited modifications to their mitochondrial fluxes, i.e. oxygen consumption, ATP synthesis, reactive oxygen species generation (ROS) and associated ratios, such as the electron leak (% ROS/O) and the oxidative cost of ATP production (% ROS/ATP). This was done at different steady state rate of oxidative phosphorylation in both pectoralis (glycolytic) and gastrocnemius (oxidative) muscles. Fasting induced a decrease in the rates of oxidative phosphorylation and maximal ROS release. All these changes were completely reversed by 3 days of refeeding. Yet, the fundamental finding of the present study is the existence of a clear threshold in ROS release and associated ratios, which remained low until a low level of mitochondrial activity is reached (30-40% of maximal oxidative phosphorylation activity).