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

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journal contribution
posted on 2023-06-10, 05:09 authored by Marten Szibor, Christina Schenkl, Mario R O Barsottini, Luke Young, Anthony Moore
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Biochemical Journal

ISSN

0264-6021

Publisher

Portland Press Ltd.

Issue

12

Volume

479

Page range

1337-1359

Event location

England

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2022-10-18

First Open Access (FOA) Date

2022-10-18

First Compliant Deposit (FCD) Date

2022-10-18