What to do with low O₂: Redox adaptations in vertebrates native to hypoxic environments

Reactive oxygen species (ROS) are important cellular signalling molecules but sudden changes in redox balance can be deleterious to cells and lethal to the whole organism. ROS production is inherently linked to environmental oxygen availability and many species live in variable oxygen environments that can range in both severity and duration of hypoxic exposure. Given the importance of redox homeostasis to cell and animal viability, it is not surprising that early studies in species adapted to various hypoxic niches have revealed diverse strategies to limit or mitigate deleterious ROS changes. Although research in this area is in its infancy, patterns are beginning to emerge in the suites of adaptations to different hypoxic environments. This review focuses on redox adaptations (i.e., modifications of ROS production and scavenging, and mitigation of oxidative damage) in hypoxia-tolerant vertebrates across a range of hypoxic environments. In general, evidence suggests that animals adapted to chronic lifelong hypoxia are in homeostasis, and do not encounter major oxidative challenges in their homeostatic environment, whereas animals exposed to seasonal chronic anoxia or hypoxia rapidly downregulate redox balance to match a hypometabolic state and employ robust scavenging pathways during seasonal reoxygenation. Conversely, animals adapted to intermittent hypoxia exposure face the greatest degree of ROS imbalance and likely exhibit enhanced ROS-mitigation strategies. Although some progress has been made, research in this field is patchy and further elucidation of mechanisms that are protective against environmental redox challenges is imperative for a more holistic understanding of how animals survive hypoxic environments.