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1. Consistent changes in muscle phenotype and mitochondrial abundance underlie dive performance across multiple lineages of diving ducks

   https://doi.org/10.1242/jeb.247550  

   Schell, Elizabeth R; Scott, Graham R; Dawson, Neal J; Winker, Kevin; McCracken, Kevin G (August 2024, Journal of Experimental Biology)

   ABSTRACT Diving animals must sustain high muscle activity with finite oxygen (O2) to forage underwater. Studies have shown that some diving mammals exhibit changes in the metabolic phenotype of locomotory muscles compared with non-divers, but the pervasiveness of such changes across diving animals is unclear, particularly among diving birds. Here, we examined whether changes in muscle phenotype and mitochondrial abundance are associated with dive capacity across 17 species of ducks from three distinct evolutionary clades (tribes) in the subfamily Anatinae: the longest diving sea ducks, the mid-tier diving pochards and the non-diving dabblers. In the gastrocnemius (the primary swimming and diving muscle), mitochondrial volume density in both oxidative and glycolytic fiber types was 70% and 30% higher in sea ducks compared with dabblers, respectively. These differences were associated with preferential proliferation of the subsarcolemmal subfraction, the mitochondria adjacent to the cell membrane and nearest to capillaries, relative to the intermyofibrillar subfraction. Capillary density and capillary-to-fiber ratio were positively correlated with mitochondrial volume density, with no variation in the density of oxidative fiber types across tribes. In the pectoralis, sea ducks had greater abundance of oxidative fiber types than dabblers, whereas pochards were intermediate between the two. These data suggest that skeletal muscles of sea ducks have a heightened capacity for aerobic metabolism and an enhanced ability to utilize O2 stores in the blood and muscle while diving. 

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2. Evolutionary diversity of muscle OXPHOS efficiency in vitro across ectothermic vertebrates

   https://doi.org/10.1098/rspb.2025.0374  

   Mueller, Rachel Lockridge; Li_Puma, Lance C; Itgen, Michael W; Chicco, Adam J (August 2025, Proceedings of the Royal Society B: Biological Sciences)

   Oxidative metabolism meets the majority of vertebrate energy demands through the coupling of mitochondrial respiration to ATP production (OXPHOS). In endotherms, variations in OXPHOS coupling efficiency influence metabolic thermogenesis, locomotor economy and reactive oxygen species (ROS) generation. However, the extent of these variations and their functional implications in ectotherms are less clear. We measured mitochondrial oxygen consumption, ATP production and ROS production in permeabilized skeletal muscle fibres from salamanders, frogs and lizards representing ectotherm clades with low, medium and high standard metabolic rates (SMRs), respectively. Consistent with predicted associations with SMR, lizards had the highest capacities for muscle mitochondrial ATP production, while salamanders had the lowest. Unexpectedly, corresponding rates of oxygen consumption followed an opposite trend, reflecting 8.5-fold variations in OXPHOS coupling efficiency between salamanders (the lowest) and lizards (the highest). Intrinsic proton permeability of the inner mitochondrial membrane was the primary source of OXPHOS coupling variation across species, being highest in salamanders and lowest in lizards. Basal proton leak mediated by uncoupling proteins and the adenine nucleotide translocase was only seen in lizards, where it limits mitochondrial ROS production. We infer that diverse evolutionary selection pressures drive unexpectedly wide variations in muscle OXPHOS efficiency with different functional implications across ectotherm clades. 

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3. A mitohormetic response to pro-oxidant exposure in the house mouse

   https://doi.org/10.1152/ajpregu.00176.2017  

   Zhang, Yufeng; Humes, Frances; Almond, Gregory; Kavazis, Andreas N.; Hood, Wendy R. (January 2018, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology)

   Mitochondria are hypothesized to display a biphasic response to reactive oxygen species (ROS) exposure. In this study, we evaluated the time course changes in mitochondrial performance and oxidative stress in house mice following X-irradiation. Forty-eight mice were equally divided among six groups, including a nonirradiated control and five experimental groups that varied in time between X-ray exposure and euthanasia (1 h and 1, 4, 7, and 10 days after X-irradiation). We measured parameters associated with mitochondrial respiratory function and ROS emission from isolated liver and skeletal muscle mitochondria and levels of oxidative damage and antioxidants in liver, skeletal muscle, and heart tissues. Mitochondrial function dropped initially after X-irradiation but recovered quickly and was elevated 10 days after the exposure. Hydrogen peroxide production, lipid peroxidation, and protein carbonylation showed inverse U-shaped curves, with levels returning to control or lower than control, 10 days after X-irradiation. Enzymatic antioxidants and markers for mitochondrial biogenesis exhibited a tissue-specific response after irradiation. These data provide the first chronological description of the mitohormetic response after a mild dose of irradiation and highlight the protective response that cells display to ROS exposure. This study also provides valuable information and application for future mitochondrial and oxidative stress studies in numerous physiological settings. 

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4. Effects of temperature acclimation on the upper thermal tolerance of two Arctic fishes

   https://doi.org/10.1093/conphys/coae001  

   Waterbury, Carolyn R.; Sutton, Trent M.; Kelley, Amanda L.; López, J. Andrés; Raby, ed., Graham (February 2024, Conservation Physiology)

   Abstract The thermally dynamic nearshore Beaufort Sea, Alaska, is experiencing climate change-driven temperature increases. Measuring thermal tolerance of broad whitefish (Coregonus nasus) and saffron cod (Eleginus gracilis), both important species in the Arctic ecosystem, will enhance understanding of species-specific thermal tolerances. The objectives of this study were to determine the extent that acclimating broad whitefish and saffron cod to 5°C and 15°C changed their critical thermal maximum (CTmax) and HSP70 protein and mRNA expression in brain, muscle and liver tissues. After acclimation to 5°C and 15°C, the species were exposed to a thermal ramping rate of 3.4°C · h−1 before quantifying the CTmax and HSP70 protein and transcript concentrations. Broad whitefish and saffron cod acclimated to 15°C had a significantly higher mean CTmax (27.3°C and 25.9°C, respectively) than 5°C-acclimated fish (23.7°C and 23.2°C, respectively), which is consistent with trends in CTmax between higher and lower acclimation temperatures. There were species-specific differences in thermal tolerance with 15°C-acclimated broad whitefish having higher CTmax and HSP70 protein concentrations in liver and muscle tissues than saffron cod at both acclimation temperatures. Tissue-specific differences were quantified, with brain and muscle tissues having the highest and lowest HSP70 protein concentrations, respectively, for both species and acclimation temperatures. The differences in broad whitefish CTmax between the two acclimation temperatures could be explained with brain and liver tissues from 15°C acclimation having higher HSP70a-201 and HSP70b-201 transcript concentrations than control fish that remained in lab-acclimation conditions of 8°C. The shift in CTmax and HSP70 protein and paralogous transcripts demonstrate the physiological plasticity that both species possess in responding to two different acclimation temperatures. This response is imperative to understand as aquatic temperatures continue to elevate. 

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5. HOXA5 Participates in Brown Adipose Tissue and Epaxial Skeletal Muscle Patterning and in Brown Adipocyte Differentiation

   https://doi.org/10.3389/fcell.2021.632303  

   Holzman, Miriam A.; Ryckman, Abigail; Finkelstein, Tova M.; Landry-Truchon, Kim; Schindler, Kyra A.; Bergmann, Jenna M.; Jeannotte, Lucie; Mansfield, Jennifer H. (February 2021, Frontiers in Cell and Developmental Biology)

   null (Ed.)

   Brown adipose tissue (BAT) plays critical thermogenic, metabolic and endocrine roles in mammals, and aberrant BAT function is associated with metabolic disorders including obesity and diabetes. The major BAT depots are clustered at the neck and forelimb levels, and arise largely within the dermomyotome of somites, from a common progenitor with skeletal muscle. However, many aspects of BAT embryonic development are not well understood. Hoxa5 patterns other tissues at the cervical and brachial levels, including skeletal, neural and respiratory structures. Here, we show that Hoxa5 also positively regulates BAT development, while negatively regulating formation of epaxial skeletal muscle. HOXA5 protein is expressed in embryonic preadipocytes and adipocytes as early as embryonic day 12.5. Hoxa5 null mutant embryos and rare, surviving adults show subtly reduced iBAT and sBAT formation, as well as aberrant marker expression, lower adipocyte density and altered lipid droplet morphology. Conversely, the epaxial muscles that arise from a common dermomyotome progenitor are expanded in Hoxa5 mutants. Conditional deletion of Hoxa5 with Myf5/Cre can reproduce both BAT and epaxial muscle phenotypes, indicating that HOXA5 is necessary within Myf5- positive cells for proper BAT and epaxial muscle development. However, recombinase-based lineage tracing shows that Hoxa5 does not act cell-autonomously to repress skeletal muscle fate. Interestingly, Hoxa5 -dependent regulation of adipose-associated transcripts is conserved in lung and diaphragm, suggesting a shared molecular role for Hoxa5 in multiple tissues. Together, these findings establish a role for Hoxa5 in embryonic BAT development. 

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