During lean times of food scarcity, animals go all out to get the biggest bang for their energetic buck, including adjusting energy metabolism and downsizing non-essential processes such as growth and reproduction. This strategy has the immediate benefit of stretching limited energy stores, but may have hidden costs not revealed until later in life. One potential trade-off of the metabolic changes made during fasting is increased oxidative stress due to modifications to the mitochondria. These complicated organelles are critical for metabolism, but are also a major source of potentially toxic oxidants in the form of reactive oxygen species (ROS), a by-product of electron movement through the respiratory chain that supports ATP production. The dual role of mitochondria intrigued Karine Salin and her colleagues from the University of Glasgow, UK, and Semmelweis University, Hungary, so they investigated whether the metabolic adjustments made by mitochondria during fasting also caused oxidative stress in brown trout (Salmo trutta), a species that naturally experiences periods when food is scarce.
The team either fed trout fry as much as they could eat or deprived them of food in a realistic simulation of the natural food shortages experienced by these animals. After 2 weeks, the team collected the mitochondria from the fish's livers and measured how much oxygen they consumed as they produced energy-rich ATP (known as state 3 respiration) and while maintaining the electric gradient that counteracts proton leak across the mitochondrial inner membrane (state 4 respiration). The team also measured the size of the electric gradient directly using the fluorescent probe safranin.
Comparing the sizes of the livers, the team found that those from the fasted fish were about one-third the size of those from the well-fed fish and had fewer mitochondria, leading to a 50–70% reduction in respiration rate. However, the story was very different at the level of the individual mitochondria: fasted mitochondria increased state 3 respiration and reduced state 4 respiration, meaning they selectively increased their capacity to produce ATP without increasing the amount of energy dissipated through proton leakage. A larger electric gradient across the membranes of the mitochondria from the fasted fish supported these energy-saving modifications to improve the efficiency of energy transduction in the mitochondria further.
So, fasted mitochondria were more efficient, but how did this relate to the risk of oxidative stress caused by the oxygen by-products of metabolism? The team estimated the amount of oxidative stress that the mitochondria were experiencing by injecting a compound into the fish that measured the presence of one of the toxic oxygen by-products: hydrogen peroxide. The fasted mitochondria had nearly twice as much hydrogen peroxide as fed mitochondria, supporting the notion that reduced metabolism can potentially lead to oxidative stress. How this increase in stress occurred is not clear, but it could be due to the increase in the electric gradient (larger gradients are sometimes associated with high oxidative stress) or other aspects of the liver function, such as cutbacks to the system that mops up toxic oxygen by-products as an energy-saving measure.
Regardless of its root cause, increased oxidative stress could lead to long-term life-history challenges for fasted fish, such as DNA damage and ageing. This study also provides mechanistic insight into the trade-off between short-term gains from reducing metabolism during fasting and long-term costs to subsequent life-history traits.
