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Pacific hagfish (Eptatretus stoutii) are an ancient agnathan vertebrate known to be anoxia tolerant. To study their metabolic organization and the role of the mitochondria in anoxia tolerance we developed a novel protocol to measure mitochondrial function in permeabilized cardiomyocytes and how this is affected by one hour of anoxia followed by reoxygenation. When measured at 10 °C the mitochondria had a respiration rate of 2.1 ± 0.1pmol/s/mg WW during OXPHOS with saturating concentrations of glutamate, malate, and succinate. This is comparatively low compared to other ectothermic species. The functional characteristics of the mitochondria were quantified with mitochondrial control ratios. These demonstrated that proton leak contributed to just under 50% of the oxygen flux, with the remainder going towards ATP phosphorylation. Finally, when the preparations were exposed to an anoxia-reoxygenation protocol there was no difference in respiration compared to that of a heart sample from the same animal maintained under normoxia for the same time. When Complex I alone or Complex I and II were stimulated following one hour of anoxia there was no decline in oxygen flux observed. However, if Complex II was activated alone there was a significant decline in respiration. This decrease was however also observed in the mitochondria maintained in normoxia for one hour. In conclusion, Pacific hagfish cardiac mitochondria demonstrated a low rate of oxygen consumption, a loosely coupled electron transfer system, and a resistance to one hour of anoxia., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Oxidative phosphorylation is compromised in hypoxia, but many organisms live and exercise in low oxygen environments. Hypoxia-driven adaptations at the mitochondrial level are common and may enhance energetic efficiency or minimize deleterious reactive oxygen species (ROS) generation. Mitochondria from various hypoxia-tolerant animals exhibit robust functional changes following in vivo hypoxia and we hypothesized that similar plasticity would occur in naked mole-rat skeletal muscle. To test this, we exposed adult subordinate naked mole-rats to normoxia (21% O 2 ) or acute (4 h, 7% O 2 ) or chronic hypoxia (4-6 weeks, 11% O 2 ) and then isolated skeletal muscle mitochondria. Using high-resolution respirometry and a fluorescent indicator of ROS production, we then probed for changes in: i) lipid- (palmitoylcarnitine-malate), ii) carbohydrate- (pyruvate-malate), and iii) succinate-fueled metabolism, and also iv) complex IV electron transfer capacity, and v) H 2 O 2 production. Compared to normoxic values, a) lipid-fueled uncoupled respiration was reduced ~15% during acute and chronic hypoxia, b) complex I-II capacity and the rate of ROS efflux were both unaffected, and c) complex II and IV uncoupled respiration were supressed ~16% following acute hypoxia. Notably, complex II-linked H 2 O 2 efflux was 33% lower after acute hypoxia, which may reduce deleterious ROS bursts during reoxygenation. These mild changes in lipid- and carbohydrate-fueled respiratory capacity may reflect the need for this animal to exercise regularly in highly variable and intermittently hypoxic environments in which more robust plasticity may be energetically expensive., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Reversible protein acetylation is an important regulatory mechanism for modulating protein function. The cellular protein acetylome is in large part dictated by the cellular redox balance, and in particular [NAD + ]. While the relationship between hypoxia, redox balance, energy charge and resulting mitochondrial dysfunction has been examined in the context of hypoxia-linked pathologies, little is known about the direct effects of decreases in environmental oxygen on reversible lysine acetylation, and the resulting modifications to mitochondrial metabolism. To address this knowledge gap, we exposed zebrafish (Danio rerio) to 16 h of hypoxia (2.21 kPa) and quantified acetylation levels of 1220 proteins using whole-cell proteomics in samples of brain taken from normoxic and hypoxic zebrafish. In addition, we examined the effects of hypoxia on cytoplasmic and mitochondrial redox status, whole-cell energetics, the activity of the mitochondrial NAD + -dependent deacetylase SIRT3, and electron transport chain complex activities to determine if there is an association between hypoxia-induced metabolic disturbances, protein acetylation, and mitochondrial function. Our results (1) reveal several key changes in the acetylation status of proteins in the brain, primarily within the mitochondria; (2) show significant fluctuations in cytoplasmic and mitochondrial redox status within the brain during hypoxia exposure; and (3) provide evidence that lysine acetylation may be related to large changes in electron transport and ATP-synthase complex activities and adenylate status in zebrafish exposed to hypoxic stress. Together, these data provide new insights into the role of protein modifications in mitochondrial metabolism during hypoxia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Temperature fluctuations, hypoxia and metals pollution frequently occur simultaneously or sequentially in aquatic systems and their interactions may confound interpretation of their biological impacts. With a focus on energy homeostasis, the present study examined how warm acclimation influences the responses and interactions of acute temperature shift, hypoxia and copper (Cu) exposure in fish. Rainbow trout (Oncorhynchus mykiss) were acclimated to cold (11°C; control) and warm (20°C) temperature for 3 weeks followed by exposure to environmentally realistic levels of Cu and hypoxia for 24h. Subsequently, mitochondrial electron transport system (ETS) respiratory activity supported by complexes I-IV (CI-IV), plasma metabolites and condition indices were measured. Warm acclimation reduced fish condition, induced aerobic metabolism and altered the responses of fish to acute temperature shift, hypoxia and Cu. Whereas warm acclimation decelerated the ETS and increased the sensitivity of maximal oxidation rates of the proximal (CI and II) complexes to acute temperature shift, it reduced the thermal sensitivity of state 4 (proton leak). Effects of Cu with and without hypoxia were variable depending on the acclimation status and functional index. Notably, Cu stimulated respiratory activity in the proximal ETS segments, while hypoxia was mostly inhibitory and minimized the stimulatory effect of Cu. The effects of Cu and hypoxia were modified by temperature and showed reciprocal antagonistic interaction on the ETS and plasma metabolites, with modest additive actions limited to CII and IV state 4. Overall, our results indicate that warm acclimation came at a cost of reduced ETS efficiency and increased sensitivity to added stressors., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In aerobic conditions, the proton-motive force drives oxidative phosphorylation (OXPHOS) and the conversion of ADP to ATP. In hypoxic environments, OXPHOS is impaired, resulting in energy shortfalls and the accumulation of protons and lactate. This results in cellular acidification, which may impact the activity and/or integrity of mitochondrial enzymes and in turn negatively impact mitochondrial respiration and thus aerobic ATP production. Naked mole-rats (NMRs) are among the most hypoxia-tolerant mammals and putatively experience intermittent hypoxia in their underground burrows. However, if and how NMR cardiac mitochondria are impacted by lactate accumulation in hypoxia is unknown. We predicted that lactate alters mitochondrial respiration in NMR cardiac muscle. To test this, we used high-resolution respirometry to measure mitochondrial respiration in permeabilized cardiac muscle fibres from NMRs exposed to 4 h of in vivo normoxia (21% O2) or hypoxia (7% O2). We found that: (1) cardiac mitochondria cannot directly oxidize lactate, but surprisingly, (2) lactate inhibits mitochondrial respiration, and (3) decreases complex IV maximum respiratory capacity. Finally, (4) in vivo hypoxic exposure decreases the magnitude of lactate-mediated inhibition of mitochondrial respiration. Taken together, our results suggest that lactate may retard electron transport system function in NMR cardiac mitochondria, particularly in normoxia, and that NMR hearts may be primed for anaerobic metabolism. [ABSTRACT FROM AUTHOR]

In plants, flooding-induced oxygen deficiency causes severe stress, leading to growth reduction and yield loss. It is therefore important to understand the molecular mechanisms for adaptation to hypoxia. Aquaporins at the plasma membrane play a crucial role in water uptake. However, their role during hypoxia and membrane redox changes is still not fully understood. The influence of 24 h hypoxia induction on hydroponically grown maize (Zea mays L.) was investigated using an oil-based setup. Analyses of physiological parameters revealed typical flooding symptoms such as increased ethylene and H2O2 levels, an increased alcohol dehydrogenase activity, and an increased redox activity at the plasma membrane along with decreased oxygen of the medium. Transcriptomic analysis and shotgun proteomics of plasma membranes and soluble fractions were performed to determine alterations in maize roots. RNA-sequencing data confirmed the upregulation of genes involved in anaerobic metabolism, biosynthesis of the phytohormone ethylene, and its receptors. Transcripts of several antioxidative systems and other oxidoreductases were regulated. Mass spectrometry analysis of the plasma membrane proteome revealed alterations in redox systems and an increased abundance of aquaporins. Here, we discuss the importance of plasma membrane aquaporins and redox systems in hypoxia stress response, including the regulation of plant growth and redox homeostasis. [ABSTRACT FROM AUTHOR]

In plants, flooding-induced oxygen deficiency causes severe stress, leading to growth reduction and yield loss. It is therefore important to understand the molecular mechanisms for adaptation to hypoxia. Aquaporins at the plasma membrane play a crucial role in water uptake. However, their role during hypoxia and membrane redox changes is still not fully understood. The influence of 24 h hypoxia induction on hydroponically grown maize (Zea mays L.) was investigated using an oil-based setup. Analyses of physiological parameters revealed typical flooding symptoms such as increased ethylene and H2O2 levels, an increased alcohol dehydrogenase activity, and an increased redox activity at the plasma membrane along with decreased oxygen of the medium. Transcriptomic analysis and shotgun proteomics of plasma membranes and soluble fractions were performed to determine alterations in maize roots. RNA-sequencing data confirmed the upregulation of genes involved in anaerobic metabolism, biosynthesis of the phytohormone ethylene, and its receptors. Transcripts of several antioxidative systems and other oxidoreductases were regulated. Mass spectrometry analysis of the plasma membrane proteome revealed alterations in redox systems and an increased abundance of aquaporins. Here, we discuss the importance of plasma membrane aquaporins and redox systems in hypoxia stress response, including the regulation of plant growth and redox homeostasis.