A Comparison of the mitochondrial performance between migratory and sedentary mimid thrushes.

Birds exhibit a variety of migration strategies. Because sustained flapping flight requires the production of elevated levels of energy compared to typical daily activities, migratory birds are well-documented to have several physiological adaptations to support the energy demands of migration. However, even though mitochondria are the source of ATP that powers flight, the respiratory performance of the mitochondria is almost unstudied in the context of migration. We hypothesized that migratory species would have higher mitochondrial respiratory performance during migration compared to species that do not migrate. To test this hypothesis, we compared variables related to mitochondrial respiratory function between two confamilial bird species-the migratory Gray Catbird (Dumetella carolinensis) and the non-migratory Northern Mockingbird (Mimus polyglottos). Birds were captured at the same location along the Alabama Gulf Coast, where we assumed that Gray Catbirds were migrants and where resident Northern Mockingbirds live year-round. We found a trend in citrate synthase activity, which suggests that Gray Catbirds have a greater mitochondrial volume in their pectoralis muscle, but we observed no other differences in mitochondrial respiration or complex enzymatic activities between individuals from the migrant versus the non-migrant species. However, when we assessed the catbirds included in our study using well-established indicators of migratory physiology, birds fell into two groups: a group with physiological parameters indicating a physiology of birds engaged in migration and a group with the physiology of birds not migrating. Thus, our comparison included catbirds that appeared to be outside of migratory condition. When we compared the mitochondrial performance of these three groups, we found that the mitochondrial respiratory capacity of migrating catbirds was very similar to that of Northern Mockingbirds, while the catbirds judged to be not migrating were lowest. One explanation for these observations is these species display very different daily flight behaviors. While the mockingbirds we sampled were not breeding nor migrating, they are highly active birds, living in the open and engaging in flapping flights throughout each day. In contrast, Gray Catbirds live in shrubs and fly infrequently when not migrating. Such differences in baseline energy needs likely confounded our attempt to study adaptations to migration.

Balancing Act: an Interdisciplinary Exploration of Trade-offs in Reproducing Females.

Trade-offs resulting from the high demand of offspring production are a central focus of many subdisciplines within the field of biology. Yet, despite the historical and current interest on this topic, large gaps in our understanding of whole-organism trade-offs that occur in reproducing individuals remain, particularly as it relates to the nuances associated with female reproduction. This volume of Integrative and Comparative Biology (ICB) contains a series of papers that focus on reviewing trade-offs from the female-centered perspective of biology (i.e., a perspective that places female reproductive biology at the center of the topic being investigated or discussed). These papers represent some of the work showcased during our symposium held at the 2024 meeting of the Society for Integrative and Comparative Biology (SICB) in Seattle, Washington. In this roundtable discussion, we use a question-and-answer format to capture the diverse perspectives and voices involved in our symposium. We hope that the dialogue featured in this discussion will be used to motivate researchers interested in understanding trade-offs in reproducing females and provide guidance on future research endeavors.

Mechanisms that Alter Capacity for ATP Production and OXPHOS: Insights from Avian Migration.

Avian migration is among the most energetically demanding feats observed in animals. Studies evaluating the physiological underpinnings of migration have repeatedly shown that migratory birds display numerous adaptations that ultimately supply the flight muscle mitochondria with abundant fuel and oxygen during long-distance flights. To make use of this high input, the organs and mitochondria of migrants are predicted to display several traits that maximize their capacity to produce adenosine triphosphate (ATP). This review aims to introduce readers to several mechanisms by which organs and mitochondria can alter their capacity for oxidative phosphorylation and adenosine triphosphate production. The role of organ size, mitochondrial volume, substrate, and oxygen delivery to the electron transport system are discussed. A central theme of this review is the role of changes in electron chain complex activity, mitochondrial morphology and dynamics, and supercomplexes in allowing avian migrants and other taxa to alter the performance of the electron transport system with predictable shifts in demand. It is my hope that this review will serve as a springboard for future studies exploring the mechanisms that alter bioenergetic capacity across animal species.

A Mitochondrial Perspective on the Demands of Reproduction.

The cost of supporting traits that increase mating opportunities and maximize the production of quality offspring is paid in energy. This currency of reproduction is enabled by bioenergetic adaptations that underlie the flexible changes in energy utilization that occur with reproduction. This review considers the traits that contribute to variation in the capacity of an organ to produce ATP. Further, it synthesizes findings from studies that have evaluated bioenergetic adaptations to the production of sexually selected traits and performance during reproduction and the role of change in mitochondrial respiratory performance in the tradeoff between reproduction and longevity. Cumulatively, these works provide evidence that in selecting for redder males, female finches will likely mate with a male with high mitochondrial respiratory performance and, potentially, a higher probability of mitonuclear compatibility. Females from diverse taxa allocate more to reproduction when the respiratory performance of mitochondria or density of the inner mitochondrial membrane in the liver or skeletal muscle is higher. Finally, reproduction does not appear to have persistent negative effects on mitochondrial respiratory performance, countering a role for mitochondria in the trade-off between reproduction and longevity. I close by noting that adaptations that improve mitochondrial respiratory performance appear vital for optimizing reproductive fitness.

Flexibility underlies differences in mitochondrial respiratory performance between migratory and non-migratory White-crowned Sparrows (Zonotrichia leucophrys).

Migration is one of the most energy-demanding behaviors observed in birds. Mitochondria are the primary source of energy used to support these long-distance movements, yet how mitochondria meet the energetic demands of migration is scarcely studied. We quantified changes in mitochondrial respiratory performance in the White-crowned Sparrow (Zonotrichia leucophrys), which has a migratory and non-migratory subspecies. We hypothesized that the long-distance migratory Gambel's subspecies (Z. l. gambelii) would show higher mitochondrial respiratory performance compared to the non-migratory Nuttall's subspecies (Z. l. nuttalli). We sampled Gambel's individuals during spring pre-migration, active fall migration, and a period with no migration or breeding (winter). We sampled Nuttall's individuals during periods coinciding with fall migration and the winter period of Gambel's annual cycle. Overall, Gambel's individuals had higher citrate synthase, a proxy for mitochondrial volume, than Nuttall's individuals. This was most pronounced prior to and during migration. We found that both OXPHOS capacity (state 3) and basal respiration (state 4) of mitochondria exhibit high seasonal flexibility within Gambel's individuals, with values highest during active migration. These values in Nuttall's individuals were most similar to Gambel's individuals in winter. Our observations indicate that seasonal changes in mitochondrial respiration play a vital role in migration energetics.

Mitochondrial stress in the spaceflight environment.

Space is a challenging environment that deregulates individual homeostasis. The main external hazards associated with spaceflight include ionizing space radiation, microgravity, isolation and confinement, distance from Earth, and hostile environment. Characterizing the biological responses to spaceflight environment is essential to validate the health risks, and to develop effective protection strategies. Mitochondria energetics is a key mechanism underpinning many physiological, ecological and evolutionary processes. Moreover, mitochondrial stress can be considered one of the fundamental features of space travel. So, we attempt to synthesize key information regarding the extensive effects of spaceflight on mitochondria. In summary, mitochondria are affected by all of the five main hazards of spaceflight at multiple levels, including their morphology, respiratory function, protein, and genetics, in various tissues and organ systems. We emphasize that investigating mitochondrial biology in spaceflight conditions should become the central focus of research on the impacts of spaceflight on human health, as this approach will help resolve numerous challenges of space health and combat several health disorders associated with mitochondrial dysfunction.

Understanding Patterns of Life History Trait Covariation in an Untapped Resource, the Lab Mouse.

AbstractThrough artificial selection and inbreeding, strains of laboratory mice have been developed that vary in the expression of a single or suite of desired traits valuable to biomedical research. In addition to the selected trait(s), these strains also display variation in pelage color, body size, physiology, and life history. This article exploits the broad phenotypic variation across lab mouse strains to evaluate the relationships between life history and metabolism. Life history variation tends to exist along a fast-slow continuum. There has been considerable interest in understanding the ecological and evolutionary factors underlying life history variation and the physiological and metabolic processes that support them. Yet it remains unclear how these key traits scale across hierarchical levels, as ambiguous empirical support has been garnered at the intraspecific level. Within-species investigations have been thwarted by methodological constraints and environmental factors that obscure the genetic architecture underlying the hypothesized functional integration of life history and metabolic traits. In this analysis, we used the publicly available Mouse Phenome Database by the Jackson Laboratory to investigate the relationships among life history traits (e.g., body size, reproduction, and life span) and metabolic traits (e.g., daily energy expenditure and insulin-like growth factor 1 concentration). Our findings revealed significant variation in reproductive characteristics across strains of mice as well as relationships among life history and metabolic traits. We found evidence of variation along the fast-slow life history continuum, though the direction of some relationships among these traits deviated from interspecific predictions laid out in previous literature. Furthermore, our results suggest that the strength of these relationships are strongest earlier in life.

Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.

How does density of the inner mitochondrial membrane influence mitochondrial performance?

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.

The persistent effects of corticosterone administration during lactation on the physiology of maternal and offspring mitochondria.

Reproduction and environmental stressors are generally thought to be associated with a cost to the individual experiencing them, but the physiological mechanisms mediating costs of reproduction and maternal effects remain poorly understood. Studies examining the effects of environmental stressors on a female's physiological state and body condition during reproduction, as well as the physiological condition of offspring, have yielded equivocal results. Mitochondrial physiology and oxidative stress have been implicated as important mediators of life-history trade-offs. The goal of this investigation was to uncover the physiological mechanisms responsible for the enhanced trade-off between self-maintenance and offspring investment when an animal is exposed to stressful conditions during reproduction. To that end, we manipulated circulating corticosterone (CORT) levels by orally supplementing lactating female mice with CORT and investigated mitochondrial physiology and oxidative stress of both the reproductive females and their young. We found that maternal CORT exposure resulted in lower litter mass at weaning, but mitochondrial performance and oxidative status of females were not impacted. We also found potential beneficial effects of maternal CORT on mitochondrial function (e.g. higher respiratory control ratio) and oxidative stress (e.g. lower reactive oxygen species production) of offspring in adulthood, suggesting that elevated maternal CORT may be a signal for early-life adversity and prepare the organism with a predictive, adaptive response to future stressors.

Flying on empty: reduced mitochondrial function and flight capacity in food-deprived monarch butterflies.

Mitochondrial function is fundamental to organismal performance, health and fitness - especially during energetically challenging events, such as migration. With this investigation, we evaluated mitochondrial sensitivity to ecologically relevant stressors. We focused on an iconic migrant, the North American monarch butterfly (Danaus plexippus), and examined the effects of two stressors: 7 days of food deprivation and infection by the protozoan parasite Ophryocystis elektroscirrha (known to reduce survival and flight performance). We measured whole-animal resting metabolic rate (RMR) and peak flight metabolic rate, and mitochondrial respiration of isolated mitochondria from the flight muscles. Food deprivation reduced mass-independent RMR and peak flight metabolic rate, whereas infection did not. Fed monarchs used mainly lipids in flight (respiratory quotient 0.73), but the respiratory quotient dropped in food-deprived individuals, possibly indicating switching to alternative energy sources, such as ketone bodies. Food deprivation decreased mitochondrial maximum oxygen consumption but not basal respiration, resulting in lower respiratory control ratio (RCR). Furthermore, food deprivation decreased mitochondrial complex III activity, but increased complex IV activity. Infection did not result in any changes in these mitochondrial variables. Mitochondrial maximum respiration rate correlated positively with mass-independent RMR and flight metabolic rate, suggesting a link between mitochondria and whole-animal performance. In conclusion, low food availability negatively affects mitochondrial function and flight performance, with potential implications for migration, fitness and population dynamics. Although previous studies have reported poor flight performance in infected monarchs, we found no differences in physiological performance, suggesting that reduced flight capacity may be due to structural differences or low energy stores.

A combination of red structural and pigmentary coloration in the eyespot of a copepod.

While the specific mechanisms of colour production in biological systems are diverse, the mechanics of colour production are straightforward and universal. Colour is produced through the selective absorption of light by pigments, the scattering of light by nanostructures or a combination of both. When Tigriopus californicus copepods were fed a carotenoid-limited diet of yeast, their orange-red body coloration became faint, but their eyespots remained unexpectedly bright red. Raman spectroscopy indicated a clear signature of the red carotenoid pigment astaxanthin in eyespots; however, refractive index matching experiments showed that eyespot colour disappeared when placed in ethyl cinnamate, suggesting a structural origin for the red coloration. We used transmission electron microscopy to identify consecutive nanolayers of spherical air pockets that, when modelled as a single thin film layer, possess the correct periodicity to coherently scatter red light. We then performed microspectrophotometry to quantify eyespot coloration and confirmed a distinct colour difference between the eyespot and the body. The observed spectral reflectance from the eyespot matched the reflectance predicted from our models when considering the additional absorption by astaxanthin. Together, this evidence suggests the persistence of red eyespots in copepods is the result of a combination of structural and pigmentary coloration.

Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation.

Mammals differ more than 100-fold in maximum lifespan. Here, we conducted comparative transcriptomics on 26 species with diverse lifespans. We identified thousands of genes with expression levels negatively or positively correlated with a species' maximum lifespan (Neg- or Pos-MLS genes). Neg-MLS genes are primarily involved in energy metabolism and inflammation. Pos-MLS genes show enrichment in DNA repair, microtubule organization, and RNA transport. Expression of Neg- and Pos-MLS genes is modulated by interventions, including mTOR and PI3K inhibition. Regulatory networks analysis showed that Neg-MLS genes are under circadian regulation possibly to avoid persistent high expression, whereas Pos-MLS genes are targets of master pluripotency regulators OCT4 and NANOG and are upregulated during somatic cell reprogramming. Pos-MLS genes are highly expressed during embryogenesis but significantly downregulated after birth. This work provides targets for anti-aging interventions by defining pathways correlating with longevity across mammals and uncovering circadian and pluripotency networks as central regulators of longevity.

Postnatal expression of IGF2 is the norm in amniote vertebrates.

The insulin and insulin-like signalling (IIS) network plays an important role in mediating several life-history traits, including growth, reproduction and senescence. Although insulin-like growth factors (IGFs) 1 and 2 are both key hormones in the vertebrate IIS network, research on IGF2 in juveniles and adults has been largely neglected because early biomedical research on rodents found negligible IGF2 postnatal expression. Here, we challenge this assumption and ask to what degree IGF2 is expressed during postnatal life across amniotes by quantifying the relative gene expression of IGF1 and IGF2 using publicly available RNAseq data for 82 amniote species and quantitative polymerase chain reaction on liver cDNA at embryonic, juvenile and adult stages for two lizard, bird and mouse species. We found that (i) IGF2 is expressed postnatally across amniote species and life stages-often at a higher relative expression than IGF1, contradicting rodent models; (ii) the lack of rodent postnatal IGF2 expression is due to phylogenetic placement, not inbreeding or artificial selection; and (iii) adult IGF2 expression is sex-biased in some species. Our results demonstrate that IGF2 expression is typical for amniotes throughout life, suggesting that a comprehensive understanding of the mechanisms mediating variation in life-history traits will require studies that measure both IGFs.

Short and long-term effect of reproduction on mitochondrial dynamics and autophagy in rats.

We evaluated mitochondrial dynamics and autophagy by investigating the acute and long-term changes in the liver and skeletal muscle of rats in multiple reproductive stages. A total of 48 rats were used. Rats were randomly assigned to three groups (n = 16 per group): nonreproductive females; females that became pregnant, gave birth, but had their pups removed at birth, and thus, did not lactate; and females that experienced pregnancy, gave birth, and were allowed to lactate. Each group was further divided into two-time subgroups (n = 8 per subgroup) and data were collected at a time-point corresponding to 1) peak lactation (day 14 of lactation) in the lactating animals (4 months of age) and 2) 15 weeks after parturition (12 weeks post-weaning in lactating animals; 7 months of age). Levels of several proteins involved in mitochondrial dynamics and the autophagy system were measured in the liver and skeletal muscle. Beclin1 protein levels in the liver were higher in non-lactating rats two weeks after parturition, while Beclin1 protein levels were highest in 7-month-old animals that had previously experienced a standard reproductive event that included pregnancy and a full 3 week of lactation. These animals also exhibited higher protein levels of the mitochondrial fusion marker Mfn2 in the liver. In skeletal muscle, we also observed increased protein levels of the mitochondrial fission marker DRP1 in non-lactating animals compared to animals that lactated. In summary, our data provide insightful information on the mechanisms that influence liver and skeletal muscle remodeling in response to the metabolic challenges of reproduction, and lactation in particular. Autophagy remodeling and mitochondrial fusion seem to coincide with liver mass size during the lactation stage of reproduction. Our findings highlight the complex changes that occur in the liver and skeletal muscle during reproduction, and highlights the remarkable plasticity required during this demanding metabolic feat.

Development of a Mobile Mitochondrial Physiology Laboratory for Measuring Mitochondrial Energetics in the Field.

Mitochondrial energetics is a central theme in animal biochemistry and physiology, with researchers using mitochondrial respiration as a metric to investigate metabolic capability. To obtain the measures of mitochondrial respiration, fresh biological samples must be used, and the entire laboratory procedure must be completed within approximately 2 h. Furthermore, multiple pieces of specialized equipment are required to perform these laboratory assays. This creates a challenge for measuring mitochondrial respiration in the tissues of wild animals living far from physiology laboratories as live tissue cannot be preserved for very long after collection in the field. Moreover, transporting live animals over long distances induces stress, which can alter mitochondrial energetics. This manuscript introduces the Auburn University (AU) MitoMobile, a mobile mitochondrial physiology laboratory that can be taken into the field and used on-site to measure mitochondrial metabolism in tissues collected from wild animals. The basic features of the mobile laboratory and the step-by-step methods for measuring isolated mitochondrial respiration rates are presented. Additionally, the data presented validate the success of outfitting the mobile mitochondrial physiology laboratory and making mitochondrial respiration measurements. The novelty of the mobile laboratory lies in the ability to drive to the field and perform mitochondrial measurements on the tissues of animals captured on site.

Mitochondrial Bioenergetics of Extramammary Tissues in Lactating Dairy Cattle.

Lactation is physiologically demanding, requiring increased nutrient and energy use. Mammary and extramammary tissues undergo metabolic changes for lactation. Although it has long been recognized that mitochondria play a critical role in lactation, the mitochondrial adaptations for milk synthesis in supporting tissues, such as liver and skeletal muscle are relatively understudied. In this study, we assessed the mitochondrial function in these tissues across lactation in dairy cattle. Tissue biopsies were taken at 8 ± 2 d (early, n = 11), 75 ± 4 d (peak, n = 11) and 199 ± 6 d (late, n = 11) in milk. Early lactation biopsies were harvested from one group of cows and the peak and late biopsies from a second cohort. Milk yield (MY) was recorded at each milking and milk samples were collected for composition analysis. Mitochondrial efficiency was quantified as the respiratory control ratio (RCR), comparing maximal to resting respiration rates. Liver complex II RCR was positively associated with MY. Liver ROS emission increased across lactation whereas liver antioxidant activity was similar across lactation. No change was detected in skeletal muscle RCR or ROS emission, but muscle GPx activity decreased across lactation and muscle SOD was negatively associated with MY. Muscle oxidative damage was elevated at early and late lactation. Across lactation, genes involved in mitochondrial biogenesis were upregulated in the liver. Our results indicate that during lactation, liver mitochondrial biogenesis and efficiency are increased, which is associated with greater milk yield. In contrast, the mitochondrial efficiency in skeletal muscle remains consistent across lactation, but undergoes oxidative damage, which is associated with reduced antioxidant activity.

Effects of a Bacterial Infection on Mitochondrial Function and Oxidative Stress in a Songbird.

AbstractAs a major physiological mechanism involved in cellular renewal and repair, immune function is vital to the body's capacity to support tissue maintenance and organismal survival. Because immune defenses can be energetically expensive, the activities of metabolically active organs, such as the liver, are predicted to increase during infection by most pathogens. However, some pathogens are immunosuppressive, which might reduce the metabolic capacities of select organs to suppress immune response. Mycoplasma gallisepticum (MG) is a well-known immunosuppressive bacterium that infects domestic chickens and turkeys as well as songbirds. In the house finch (Haemorhous mexicanus), which is the primary host for MG among songbird species, MG infects both the respiratory system and the conjunctiva of the eye, causing conspicuous swelling. To study the effect of a systemic bacterial infection on cellular respiration and oxidative damage in the house finch, we measured mitochondrial respiration, mitochondrial membrane potential, reactive oxygen species production, and oxidative damage in the livers of house finches that were wild caught and either infected with MG, as indicated by genetic screening for the pathogen, or free of MG infection. We observed that MG-infected house finches showed significantly lower oxidative lipid and protein damage in liver tissue compared with their uninfected counterparts. Moreover, using complex II substrates, we documented a nonsignificant trend for lower state 3 respiration of liver mitochondria in MG-infected house finches compared with uninfected house finches (P=0.07). These results are consistent with the hypothesis that MG suppresses organ function in susceptible hosts.

Integrating Mitochondrial Aerobic Metabolism into Ecology and Evolution.

Biologists have long appreciated the critical role that energy turnover plays in understanding variation in performance and fitness among individuals. Whole-organism metabolic studies have provided key insights into fundamental ecological and evolutionary processes. However, constraints operating at subcellular levels, such as those operating within the mitochondria, can also play important roles in optimizing metabolism over different energetic demands and time scales. Herein, we explore how mitochondrial aerobic metabolism influences different aspects of organismal performance, such as through changing adenosine triphosphate (ATP) and reactive oxygen species (ROS) production. We consider how such insights have advanced our understanding of the mechanisms underpinning key ecological and evolutionary processes, from variation in life-history traits to adaptation to changing thermal conditions, and we highlight key areas for future research.

Evaluating endoplasmic reticulum stress and unfolded protein response through the lens of ecology and evolution.

Considerable progress has been made in understanding the physiological basis for variation in the life-history patterns of animals, particularly with regard to the roles of oxidative stress and hormonal regulation. However, an underappreciated and understudied area that could play a role in mediating inter- and intraspecific variation of life history is endoplasmic reticulum (ER) stress, and the resulting unfolded protein response (UPRER ). ER stress response and the UPRER maintain proteostasis in cells by reducing the intracellular load of secretory proteins and enhancing protein folding capacity or initiating apoptosis in cells that cannot recover. Proper modulation of the ER stress response and execution of the UPRER allow animals to respond to intracellular and extracellular stressors and adapt to constantly changing environments. ER stress responses are heritable and there is considerable individual variation in UPRER phenotype in animals, suggesting that ER stress and UPRER phenotype can be subjected to natural selection. The variation in UPRER phenotype presumably reflects the way animals respond to ER stress and environmental challenges. Most of what we know about ER stress and the UPRER in animals has either come from biomedical studies using cell culture or from experiments involving conventional laboratory or agriculturally important models that exhibit limited genetic diversity. Furthermore, these studies involve the assessment of experimentally induced qualitative changes in gene expression as opposed to the quantitative variations that occur in naturally existing populations. Almost all of these studies were conducted in controlled settings that are often quite different from the conditions animals experience in nature. Herein, we review studies that investigated ER stress and the UPRER in relation to key life-history traits including growth and development, reproduction, bioenergetics and physical performance, and ageing and senescence. We then ask if these studies can inform us about the role of ER stress and the UPRER in mediating the aforementioned life-history traits in free-living animals. We propose that there is a need to conduct experiments pertaining to ER stress and the UPRER in ecologically relevant settings, to characterize variation in ER stress and the UPRER in free-living animals, and to relate the observed variation to key life-history traits. We urge others to integrate multiple physiological systems and investigate how interactions between ER stress and oxidative stress shape life-history trade-offs in free-living animals.