Decreased mitochondrial metabolic requirements in fasting animals carry an oxidative cost

Abstract

Summary Many animals experience periods of food shortage in their natural environment. It has been hypothesised that the metabolic responses of animals to naturally‐occurring periods of food deprivation may have long‐term negative impacts on their subsequent life‐history.In particular, reductions in energy requirements in response to fasting may help preserve limited resources but potentially come at a cost of increased oxidative stress. However, little is known about this trade‐off since studies of energy metabolism are generally conducted separately from those of oxidative stress.Using a novel approach that combines measurements of mitochondrial function with in vivo levels of hydrogen peroxide (H2O2) in brown trout (Salmo trutta), we show here that fasting induces energy savings in a highly metabolically active organ (the liver) but at the cost of a significant increase in H2O2, an important form of reactive oxygen species (ROS).After a 2‐week period of fasting, brown trout reduced their whole‐liver mitochondrial respiratory capacities (state 3, state 4 and cytochrome c oxidase activity), mainly due to reductions in liver size (and hence the total mitochondrial content). This was compensated for at the level of the mitochondrion, with an increase in state 3 respiration combined with a decrease in state 4 respiration, suggesting a selective increase in the capacity to produce ATP without a concomitant increase in energy dissipated through proton leakage. However, the reduction in total hepatic metabolic capacity in fasted fish was associated with an almost two‐fold increase in in vivo mitochondrial H2O2 levels (as measured by the MitoB probe).The resulting increase in mitochondrial ROS, and hence potential risk of oxidative damage, provides mechanistic insight into the trade‐off between the short‐term energetic benefits of reducing metabolism in response to fasting and the potential long‐term costs to subsequent life‐history traits.

Ecological and evolutionary consequences of metabolic rate plasticity in response to environmental change

“…There are also reversible changes in relative organ size (and hence metabolic rate) when animals are faced with major energetic challenges such as long-distance migrations [70] or infrequent but large meals [71,72]. Components of mitochondrial structure and function can also shift in response to changes in ATP requirement [1,73] and/or resource availability [74][75][76], with the typical response being an increase in the efficiency of ATP production (measured as ATP produced per unit consumption of oxygen) when conditions are more challenging [74,75]. However, mitochondrial responses can differ between organs (and even between muscle types) of the same individual [74,77], and increases in mitochondrial efficiency can come at a cost of increased rates of ROS production, which may explain why ATP production efficiency is not always maximized [76].…”

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

“…Studies have shown that moderate energy restriction enhances resistance to oxidative stress and increases the mean and maximum healthy lifespan in many organisms (Sohal et al, 1994;López-Torres et al, 2002;Bevilacqua et al, 2004;Bevilacqua et al, 2005;Fontana et al, 2010;Walsh et al, 2014). In contrast, an extreme reduction in available energy such as that during fasting may induce pro-oxidant effects including, in some incidents, enhanced mitochondrial ROS production or free electron leak (ROS/O), and their subsequent negative impact on cellular integrity and life span (Sorensen et al, 2006;Fontana et al, 2010;Brown and Staples, 2011;Salin et al, 2018).…”

Sperm telomere length correlates with blood telomeres and body size in red‐sided garter snakes,Thamnophis sirtalis parietalis

“…Longer-lived snake species have lower ROS production (Robert, Brunet-Rossinni, & Bronikowski, 2007), and long-versus short-lived ecotypes of Thamnophis elegans exhibit divergence in mitochondrial genes of the electron transport chain (Schwartz, Arendsee, & Bronikowski, 2015), a principle site of ROS production (Turrens, 2003). Indeed, the few studies to investigate aphagous animals suggest fasting induces a pro-oxidant state [elephant seals (Sharick et al, 2015); fish (Morales et al, 2004, Morales et al 2011, Pascual et al, 2003, Salin et al, 2018; King penguins (Schull et al, 2016); rats (Sorensen et al, 2006)]. Given the relatively long turnover rate of blood cells in general (e.g.…”