Animals display tremendous variation in their rates of growth, reproductive output, and longevity. While the physiological and molecular mechanisms that underlie this variation remain poorly understood, the performance of the mitochondrion has emerged as a key player. Mitochondria not only impact the performance of eukaryotes via their capacity to produce ATP, but they also play a role in producing heat and reactive oxygen species and function as a major signaling hub for the cell. The papers included in this special issue emerged from a symposium titled “Inside the Black Box: The Mitochondrial Basis of Life-history Variation and Animal Performance.” Based on studies of diverse animal taxa, three distinct themes emerged from these papers. (1) When linking mitochondrial function to components of fitness, it is crucial that mitochondrial assays are performed in conditions as close as the intracellular conditions experienced by the mitochondria in vivo. (2) Functional plasticity allows mitochondria to retain their performance, as well as that of their host, over a range of exogenous conditions, and selection on mitochondrial and nuclear-derived proteins can optimize the match between the environment and the bioenergetic capacity of the mitochondrion. Finally, (3) studies of wild and wild-derived animals suggest that mitochondria play a central role in animal performance and life history strategy. Taken as a whole, we hope that these papers will foster discussion and inspire new hypotheses and innovations that will further our understanding of the mitochondrial processes that underlie variation in life history traits and animal performance.

Oxidative damage is predicted to be a mediator of trade-offs between current reproduction and future reproduction or survival, but most studies fail to support such predictions. We suggest that two factors underlie the equivocal nature of these findings: (1) investigators typically assume a negative linear relationship between current reproduction and future reproduction or survival, even though this is not consistently shown by empirical studies; and (2) studies often fail to target mechanisms that could link interactions between sequential life-history events. Here, we review common patterns of reproduction, focusing on the relationships between reproductive performance, survival and parity in females. Observations in a range of species show that performance between sequential reproductive events can decline, remain consistent or increase. We describe likely bioenergetic consequences of reproduction that could underlie these changes in fitness, including mechanisms that could be responsible for negative effects being ephemeral, persistent or delayed. Finally, we make recommendations for designing future studies. We encourage investigators to carefully consider additional or alternative measures of bioenergetic function in studies of life-history trade-offs. Such measures include reactive oxygen species production, oxidative repair, mitochondrial biogenesis, cell proliferation, mitochondrial DNA mutation and replication error and, importantly, a measure of the respiratory function to determine whether measured differences in bioenergetic state are associated with a change in the energetic capacity of tissues that could feasibly affect future reproduction or lifespan. More careful consideration of the life-history context and bioenergetic variables will improve our understanding of the mechanisms that underlie the life-history patterns of animals.

Evolutionary biologists have been interested in the negative interactions among life history traits for nearly a century, but the mechanisms that would create this negative interaction remain poorly understood. One variable that has emerged as a likely link between reproductive effort and longevity is oxidative stress. Specifically, it has been proposed that reproduction generates free radicals that cause oxidative stress and, in turn, oxidative stress damages cellular components and accelerates senescence. We propose that there is limited support for the hypothesis because reactive oxygen species (ROS), the free radicals implicated in oxidative damage, are not consistently harmful. With this review, we define the hormetic response of mitochondria to ROS, termed mitochondrial hormesis, and describe how to test for a mitohormetic response. We interpret existing data using our model and propose that experimental manipulations will further improve our knowledge of this response. Finally, we postulate how the mitohormetic response curve applies to variation in animal performance and longevity.

Our current understanding of variation in mitochondrial performance is incomplete. The production of ATP via oxidative phosphorylation is dependent, in part, on the structure of the inner mitochondrial membrane. Morphology of the inner membrane is crucial for the formation of the proton gradient across the inner membrane and, therefore, ATP synthesis. The inner mitochondrial membrane is dynamic, changing shape and surface area. These changes alter density (amount per volume) of the inner mitochondrial membrane within the confined space of the mitochondrion. Because the number of electron transport system proteins within the inner mitochondrial membrane changes with inner mitochondrial membrane area, a change in the amount of inner membrane alters the capacity for ATP production within the organelle. This review outlines the evidence that the association between ATP synthases, inner mitochondrial membrane density, and mitochondrial density (number of mitochondria per cell) impacts ATP production by mitochondria. Furthermore, we consider possible constraints on the capacity of mitochondria to produce ATP by increasing inner mitochondrial membrane density.

Energy allocation theory predicts that a lactating female should alter the energetic demands of its organ systems in a manner that maximizes nutrient allocation to reproduction while reducing nutrient use for tasks that are not vital to immediate survival. We posit that organ‐specific plasticity in the function of mitochondria plays a key role in mediating these energetic trade‐offs. The goal of this project was to evaluate mitochondrial changes that occur in response to lactation in two of the most energetically demanding organs in the body of a rodent, the liver and skeletal muscle. This work was conducted in wild‐derived house mice (Mus musculus) kept in seminatural enclosures that allow the mice to maintain a natural social structure and move within a home range size typical of wild mice. Tissues were collected from females at peak lactation and from age‐matched nonreproductive females. Mitochondrial respiration, oxidative damage, antioxidant, PGC‐1α, and uncoupling protein levels were compared between lactating and nonreproductive females. Our findings suggest that both liver and skeletal muscle downregulate specific antioxidant proteins during lactation. The liver, but not skeletal muscle, of lactating females displayed higher oxidative damage than nonreproductive females. The liver mass of lactating females increased, but the liver displayed no change in mitochondrial respiratory control ratio. Skeletal muscle mass and mitochondrial respiratory control ratio were not different between groups. However, the respiratory function of skeletal muscle did vary among lactating females as a function of stage of concurrent pregnancy, litter size, and mass of the mammary glands. The observed changes are predicted to increase the efficiency of skeletal muscle mitochondria, reducing the substrate demands of skeletal muscle during lactation. Differences between our results and prior studies highlight the role that an animals’ social and physical environment could play in how it adapts to the energetic demands of reproduction.