Structure and Mechanism of Action of the Alternative Quinol Oxidases

Young, Luke; May, Benjamin; Shiba, T.; Harada, Shigeharu; Inaoka, Daniel Ken; Kita, Kiyoshi; Moore, Anthony L.

doi:10.1007/978-94-017-7481-9_19

Cited by 8 publications

(15 citation statements)

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“…AOX is a single‐subunit, (non‐haem) di‐iron containing monotopic membrane protein which functions as a nonprotonmotive quinol oxidase, which is widespread in plant, fungal and protist mitochondria (but notably absent from the Plasmodium sp.) [74–76]. The activity of AOX allows ubiquinol‐linked respiration from NADH ( via mitochondrial complex I) to oxygen, bypassing the inhibition of cyt bc 1 , although at much reduced energetic efficiency.…”

Section: Alternative Qoi/qii Resistance Mechanisms In Fungal Phytopatmentioning

confidence: 99%

“…Four protons may be expected to be pumped into the IMS per 2 electrons transferred to oxygen in this alternative respiratory pathway due to the activity of protonmotive complex I alone (i.e. 4H + /2e − ) [75]. This represents a significant decrease from the 10H + /2e − yield expected for cyt bc 1 /cytochrome c oxidase‐linked respiration.…”

Section: Alternative Qoi/qii Resistance Mechanisms In Fungal Phytopatmentioning

confidence: 99%

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The cytochrome bc₁ complex as an antipathogenic target

2020

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The cytochrome bc1 complex is a key component of the mitochondrial respiratory chains of many eukaryotic microorganisms that are pathogenic for plants or humans, such as fungi responsible for crop diseases and Plasmodium falciparum, which causes human malaria. Cytochrome bc1 is an enzyme that contains two (ubi)quinone/quinol‐binding sites, which can be exploited for the development of fungicidal and chemotherapeutic agents. Here, we review recent progress in determination of the structure and mechanism of action of cytochrome bc1, and the associated development of antimicrobial agents (and associated resistance mechanisms) targeting its activity.

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Section: Alternative Qoi/qii Resistance Mechanisms In Fungal Phytopatmentioning

confidence: 99%

Section: Alternative Qoi/qii Resistance Mechanisms In Fungal Phytopatmentioning

confidence: 99%

The cytochrome bc₁ complex as an antipathogenic target

2020

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“…AOX catalyzes oxidation of ubiquinol and reduction of oxygen to water. In the reaction catalysed by AOX, unlike the cytochrome c oxidase reaction, oxygen acquires protons taken from ubiquinol but not from the mitochondrial matrix (Young et al, 2016). AOX is not inhibited by cyanides which are frequently used as inhibitors of cytochrome c oxidase.…”

Section: Introductionmentioning

confidence: 99%

“…Instead, it is inhibited by salicylhydroxamic acid and alkylated (npropyl-and octyl-are most used) gallates (Rogov et al, 2014). The enzyme contains two iron atoms incorporated to the polypeptide via coordination with carboxylic groups of glutamic acid residues (Berthold and Stenmark, 2003;Young et al, 2016). The relatives of the enzyme are plastoquinol terminal oxidase, dimetoxyquinone hydrolase, ribonucleotide reductase, and a few other proteins (Berthold and Stenmark, 2003).…”

Section: Introductionmentioning

confidence: 99%

Alternative NAD(P)H dehydrogenase and alternative oxidase: Proposed physiological roles in animals

McDonald

Gospodaryov

2019

Mitochondrion

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The electron transport systems in mitochondria of many organisms contain alternative respiratory enzymes distinct from those of the canonical respiratory system depicted in textbooks. Two of these enzymes, the alternative NADH dehydrogenase and the alternative oxidase, were of interest to a limited circle of researchers until they were envisioned as gene therapy tools for mitochondrial disease treatment. Recently, these enzymes were discovered in several animals. Here, we analyse the functioning of alternative NADH dehydrogenases and oxidases in different organisms. We propose that both enzymes ensure bioenergetic and metabolic flexibility during environmental transitions or other conditions which may compromise the operation of the canonical respiratory system.

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“…The residues lining the active site, which coordinate the diiron center (namely the 1° ligation sphere; T. brucei numbering throughout: E123, E162, E213, E266, H165 and H269), are all conserved (Shiba et al, 2013 ; Figure 2B ). In addition, Figure 2B also illustrates that residues involved in the 2° ligation sphere (N161, Y220, D265, Y246, and W247), which function in electron transport and the oxygen reduction cycle are also conserved in the Blastocystis sequence (Affourtit et al, 2002 ; Moore and Albury, 2008 ; Young et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

The Human Gut Colonizer Blastocystis Respires Using Complex II and Alternative Oxidase to Buffer Transient Oxygen Fluctuations in the Gut

Tsaousis

et al. 2018

Front. Cell. Infect. Microbiol.

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Blastocystis is the most common eukaryotic microbe in the human gut. It is linked to irritable bowel syndrome (IBS), but its role in disease has been contested considering its widespread nature. This organism is well-adapted to its anoxic niche and lacks typical eukaryotic features, such as a cytochrome-driven mitochondrial electron transport. Although generally considered a strict or obligate anaerobe, its genome encodes an alternative oxidase. Alternative oxidases are energetically wasteful enzymes as they are non-protonmotive and energy is liberated in heat, but they are considered to be involved in oxidative stress protective mechanisms. Our results demonstrate that the Blastocystis cells themselves respire oxygen via this alternative oxidase thereby casting doubt on its strict anaerobic nature. Inhibition experiments using alternative oxidase and Complex II specific inhibitors clearly demonstrate their role in cellular respiration. We postulate that the alternative oxidase in Blastocystis is used to buffer transient oxygen fluctuations in the gut and that it likely is a common colonizer of the human gut and not causally involved in IBS. Additionally the alternative oxidase could act as a protective mechanism in a dysbiotic gut and thereby explain the absence of Blastocystis in established IBS environments.

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Structure and Mechanism of Action of the Alternative Quinol Oxidases

Cited by 8 publications

References 50 publications

The cytochrome bc₁ complex as an antipathogenic target

The cytochrome bc₁ complex as an antipathogenic target

Alternative NAD(P)H dehydrogenase and alternative oxidase: Proposed physiological roles in animals

The Human Gut Colonizer Blastocystis Respires Using Complex II and Alternative Oxidase to Buffer Transient Oxygen Fluctuations in the Gut

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Structure and Mechanism of Action of the Alternative Quinol Oxidases

Cited by 8 publications

References 50 publications

The cytochrome bc1 complex as an antipathogenic target

The cytochrome bc1 complex as an antipathogenic target

Alternative NAD(P)H dehydrogenase and alternative oxidase: Proposed physiological roles in animals

The Human Gut Colonizer Blastocystis Respires Using Complex II and Alternative Oxidase to Buffer Transient Oxygen Fluctuations in the Gut

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Product

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The cytochrome bc₁ complex as an antipathogenic target

The cytochrome bc₁ complex as an antipathogenic target