What physiological role(s) does the alternative oxidase perform in animals?

Jacobs, Howard T.; Ballard, J. William O.

doi:10.1016/j.bbabio.2022.148556

Cited by 14 publications

(9 citation statements)

References 73 publications

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“…Furthermore, it mitigates the detrimental phenotypic effects caused by the pathogenic human Aβ variant expressed in Drosophila neurons . The underlying mechanism remains elusive and will serve as a topic for future investigations . The absence of AOX in human cells has led to its exploration as a potential gene therapy tool for addressing mitochondrial dysfunctions and disorders in humans, and a variety of studies have shown the feasibility of this idea.…”

Section: Discussionmentioning

confidence: 99%

“…AOX has been identified in a wide range of animal phyla, including tunicates, gastropods, bivalve molluscs, and copepods . However, it is absent in several species, including their sister groups, three highly advanced crown groups: vertebrates, insects, and cephalopod molluscs . A hypothesis is proposed to explain that the disappearance of AOX from most animals may be associated with the locomotive activity of the organism .…”

Section: Functions Of Aoxmentioning

confidence: 99%

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Alternative Oxidase: From Molecule and Function to Future Inhibitors

Li,

Yang,

et al. 2024

ACS Omega

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In the respiratory chain of the majority of aerobic organisms, the enzyme alternative oxidase (AOX) functions as the terminal oxidase and has important roles in maintaining metabolic and signaling homeostasis in mitochondria. AOX endows the respiratory system with flexibility in the coupling among the carbon metabolism pathway, electron transport chain (ETC) activity, and ATP turnover. AOX allows electrons to bypass the main cytochrome pathway to restrict the generation of reactive oxygen species (ROS). The inhibition of AOX leads to oxidative damage and contributes to the loss of adaptability and viability in some pathogenic organisms. Although AOXs have recently been identified in several organisms, crystal structures and major functions still need to be explored. Recent work on the trypanosome alternative oxidase has provided a crystal structure of an AOX protein, which contributes to the structure−activity relationship of the inhibitors of AOX. Here, we review the current knowledge on the development, structure, and properties of AOXs, as well as their roles and mechanisms in plants, animals, algae, protists, fungi, and bacteria, with a special emphasis on the development of AOX inhibitors, which will improve the understanding of respiratory regulation in many organisms and provide references for subsequent studies of AOX-targeted inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Functions Of Aoxmentioning

confidence: 99%

Alternative Oxidase: From Molecule and Function to Future Inhibitors

Li,

Yang,

et al. 2024

ACS Omega

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“…The suggested advantage of this mitigation strategy lies in avoiding an oxidative burst response and the associated excess production of damaging ROS during frequent hypoxia-reoxygenation cycling, typical for marine sedimentary habitats ( Abele et al, 2017 ; McDonald and Gospodaryov, 2019 ). Indeed, genes encoding for AOX are mostly inherited in hypoxia-tolerant marine invertebrates ranging from sponges and cnidarians to ascidians, including marine and freshwater bivalves ( McDonald et al, 2009 ; Jacobs and Ballard, 2022 ). Inducible expression of AOX has been reported in oysters exposed to hypoxia-reoxygenation ( Sussarellu et al, 2012 ) as well as in hypoxia-exposed freshwater bivalves from Andean lakes ( Yusseppone et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A molecular perspective on the invasibility of the southern ocean benthos: The impact of hypoxia and temperature on gene expression in South American and Antarctic Aequiyoldia bivalves

Martínez

González-Aravena²,

Held³

et al. 2023

Front. Physiol.

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When an organism makes a long-distance transition to a new habitat, the associated environmental change is often marked and requires physiological plasticity of larvae, juveniles, or other migrant stages. Exposing shallow-water marine bivalves (Aequiyoldia cf. eightsii) from southern South America (SSA) and the West Antarctic Peninsula (WAP) to changes in temperature and oxygen availability, we investigated changes in gene expression in a simulated colonization experiment of the shores of a new continent after crossing of the Drake Passage, and in a warming scenario in the WAP. Bivalves from SSA were cooled from 7°C (in situ) to 4°C and 2°C (future warmed WAP conditions), WAP bivalves were warmed from 1.5°C (current summer in situ) to 4°C (warmed WAP), gene expression patterns in response to thermal stress by itself and in combination with hypoxia were measured after 10 days. Our results confirm that molecular plasticity may play a vital role for local adaptation. Hypoxia had a greater effect on the transcriptome than temperature alone. The effect was further amplified when hypoxia and temperature acted as combined stressors. The WAP bivalves showed a remarkable ability to cope with short-term exposure to hypoxia by switching to a metabolic rate depression strategy and activating the alternative oxidation pathway, whilst the SSA population showed no comparable response. In SSA, the high prevalence of apoptosis-related differentially expressed genes especially under combined higher temperatures and hypoxia indicated that the SSA Aequiyoldia are operating near their physiological limits already. While the effect of temperature per se may not represent the single most effective barrier to Antarctic colonization by South American bivalves, the current distribution patterns as well as their resilience to future conditions can be better understood by looking at the synergistic effects of temperature in conjunction with short-term exposure to hypoxia.

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“…Mitochondrial efficiency might also be affected by the activation of alternative oxidases (AOX) that transfer electrons from the Q junction to O 2 93 . This ETS branch bypasses Complexes III and IV decreasing the protonmotive force available for ATP synthesis, increasing heat production and mitigating ROS 94,95 . The AOX appears to have been lost in the evolution of vertebrates but is present in all invertebrate phyla studied to date including non‐vertebrate chordates, as well as in plants, fungi, protists, and bacteria 93 .…”

Section: Temperature Sensitivity Of the Mitochondrial Respiration And...mentioning

confidence: 99%

“…93 This ETS branch bypasses Complexes III and IV decreasing the protonmotive force available for ATP synthesis, increasing heat production and mitigating ROS. 94,95 The AOX appears to have been lost in the evolution of vertebrates but is present in all invertebrate phyla studied to date including non-vertebrate chordates, as well as in plants, fungi, protists, and bacteria. 93 In plants, AOX expression and activity is stimulated by cold 94 ; however, the relationship between the ambient temperature and AOX activity in animal ectotherms and its implications for the mitochondrial energy economy are not yet well understood 95 and require further investigation.…”

Section: Of the Mitochondrial Respiration And Efficiencymentioning

confidence: 99%

Ectotherm mitochondrial economy and responses to global warming

Sokolova

2023

Acta Physiologica

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Temperature is a key abiotic factor affecting ecology, biogeography, and evolution of species. Alterations of energy metabolism play an important role in adaptations and plastic responses to temperature shifts on different time scales. Mitochondrial metabolism affects cellular bioenergetics and redox balance making these organelles an important determinant of organismal performances such as growth, locomotion, or development. Here I analyze the impacts of environmental temperature on the mitochondrial functions (including oxidative phosphorylation, proton leak, production of reactive oxygen species(ROS), and ATP synthesis) of ectotherms and discuss the mechanisms underlying negative shifts in the mitochondrial energy economy caused by supraoptimal temperatures. Owing to the differences in the thermal sensitivity of different mitochondrial processes, elevated temperatures (beyond the species-and population-specific optimal range) cause reallocation of the electron flux and the protonmotive force (Δp) in a way that decreases ATP synthesis efficiency, elevates the relative cost of the mitochondrial maintenance, causes excessive production of ROS and raises energy cost for antioxidant defense.These shifts in the mitochondrial energy economy might have negative consequences for the organismal fitness traits such as the thermal tolerance or growth. Correlation between the thermal sensitivity indices of the mitochondria and the whole organism indicate that these traits experience similar selective pressures but further investigations are needed to establish whether there is a cause-effect relationship between the mitochondrial failure and loss of organismal performance during temperature change.

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What physiological role(s) does the alternative oxidase perform in animals?

Cited by 14 publications

References 73 publications

Alternative Oxidase: From Molecule and Function to Future Inhibitors

Alternative Oxidase: From Molecule and Function to Future Inhibitors

A molecular perspective on the invasibility of the southern ocean benthos: The impact of hypoxia and temperature on gene expression in South American and Antarctic Aequiyoldia bivalves

Ectotherm mitochondrial economy and responses to global warming

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