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 subsequently 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 carried out at different steady-state rates 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. These changes were completely reversed by 3 days of refeeding. Yet, the fundamental finding of the present study was the existence of a clear threshold in ROS release and associated ratios, which remained low until a low level of mitochondrial activity was reached (30-40% of maximal oxidative phosphorylation activity).

The effect of short-term fasting on the oxidative status of larvae of crested newt species and their hybrids

“…However, the two subsequently-activated components in this biochemical cascade, the H2O2-scavenging enzymes, failed. The absence of an adequate response from CAT and GSH-Px in removing H2O2 is in agreement with the significant increases in H2O2 concentrations that are observed during fasting in the mitochondria of different animals (Sorensen et al, 2006;Salin et al, 2018;Roussel et al, 2019). Aside from direct effects, such as oxidative damage of biomolecules, it was suggested that increased H2O2 concentration as a secondary messenger could play a role in the re-feeding signal (Sylvie et al, 2012) by modulating cellular hormesis (Costantini, 2014;Schull et al, 2016).…”

Integrating Mitochondrial Aerobic Metabolism into Ecology and Evolution

“…The shading of each region represents whether oxygen is put toward ATP production (slashed region), proton leak (filled gray region), or ROS production (unshaded region). In (A), the filled circles represent possible measurements of an animal at rest (i) or the same animal in a state of high activity (ii), informed by data in [79]. In a highly active state (ii), the high demand for ATP causes ATP synthase to rapidly use up the proton gradient, so protonmotive force and rate of proton leak become relatively low.…”

Skeletal muscle metabolism in sea-acclimatized king penguins: II. Improved efficiency of mitochondrial bioenergetics

“…This condition promotes succinate accumulation within mitochondria (Hochachka et al, 1975), and thereafter a burst of reactive oxygen species production that is associated with its rapid oxidation during post-dive reperfusion of tissues (Dröse, 2013). Again, the phosphorylating activity of mitochondria negatively regulates the ANT-mediated fatty acid-induced proton leak (Roussel et al, 1998(Roussel et al, , 2000Bertholet et al, 2019) and the release of reactive oxygen species from mitochondria (Goncalves et al, 2015;Roussel et al, 2019), which would in turn prevent the activation of UCPs. These properties indicate that the uncoupling activities of ANT and avUCP would be at a minimum under high phosphorylating activity when mitochondria are fully coupled and cellular energy demand is high, but maximum in a resting state when mitochondria are loosely coupled and cellular energy demand is low.…”