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Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?

Some of the most threatening human diseases are due to a blockage of the mitochondrial electron transport chain (ETC). In a variety of plants, fungi, and prokaryotes, there is a naturally evolved mechanism for such threats to viability, namely a bypassing of the blocked portion of the ETC by alterna...

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Autores principales: Szibor, Marten, Schenkl, Christina, Barsottini, Mario R. O., Young, Luke, Moore, Anthony L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246349/
https://www.ncbi.nlm.nih.gov/pubmed/35748702
http://dx.doi.org/10.1042/BCJ20180192
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author Szibor, Marten
Schenkl, Christina
Barsottini, Mario R. O.
Young, Luke
Moore, Anthony L.
author_facet Szibor, Marten
Schenkl, Christina
Barsottini, Mario R. O.
Young, Luke
Moore, Anthony L.
author_sort Szibor, Marten
collection PubMed
description Some of the most threatening human diseases are due to a blockage of the mitochondrial electron transport chain (ETC). In a variety of plants, fungi, and prokaryotes, there is a naturally evolved mechanism for such threats to viability, namely a bypassing of the blocked portion of the ETC by alternative enzymes of the respiratory chain. One such enzyme is the alternative oxidase (AOX). When AOX is expressed, it enables its host to survive life-threatening conditions or, as in parasites, to evade host defenses. In vertebrates, this mechanism has been lost during evolution. However, we and others have shown that transfer of AOX into the genome of the fruit fly and mouse results in a catalytically engaged AOX. This implies that not only is the AOX a promising target for combating human or agricultural pathogens but also a novel approach to elucidate disease mechanisms or, in several cases, potentially a therapeutic cure for human diseases. In this review, we highlight the varying functions of AOX in their natural hosts and upon xenotopic expression, and discuss the resulting need to develop species-specific AOX inhibitors.
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spelling pubmed-92463492022-07-12 Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism? Szibor, Marten Schenkl, Christina Barsottini, Mario R. O. Young, Luke Moore, Anthony L. Biochem J Molecular Bases of Health & Disease Some of the most threatening human diseases are due to a blockage of the mitochondrial electron transport chain (ETC). In a variety of plants, fungi, and prokaryotes, there is a naturally evolved mechanism for such threats to viability, namely a bypassing of the blocked portion of the ETC by alternative enzymes of the respiratory chain. One such enzyme is the alternative oxidase (AOX). When AOX is expressed, it enables its host to survive life-threatening conditions or, as in parasites, to evade host defenses. In vertebrates, this mechanism has been lost during evolution. However, we and others have shown that transfer of AOX into the genome of the fruit fly and mouse results in a catalytically engaged AOX. This implies that not only is the AOX a promising target for combating human or agricultural pathogens but also a novel approach to elucidate disease mechanisms or, in several cases, potentially a therapeutic cure for human diseases. In this review, we highlight the varying functions of AOX in their natural hosts and upon xenotopic expression, and discuss the resulting need to develop species-specific AOX inhibitors. Portland Press Ltd. 2022-06-24 /pmc/articles/PMC9246349/ /pubmed/35748702 http://dx.doi.org/10.1042/BCJ20180192 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Molecular Bases of Health & Disease
Szibor, Marten
Schenkl, Christina
Barsottini, Mario R. O.
Young, Luke
Moore, Anthony L.
Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
title Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
title_full Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
title_fullStr Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
title_full_unstemmed Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
title_short Targeting the alternative oxidase (AOX) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
title_sort targeting the alternative oxidase (aox) for human health and food security, a pharmaceutical and agrochemical target or a rescue mechanism?
topic Molecular Bases of Health & Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246349/
https://www.ncbi.nlm.nih.gov/pubmed/35748702
http://dx.doi.org/10.1042/BCJ20180192
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