Targeting the Alternative Oxidase (AOX) for Human Health and Food Security, a Pharmaceutical and Agrochemical Target or a Rescue Mechanism?

Overview

Journal Biochem J

Specialty Biochemistry

Date 2022 Jun 24

PMID 35748702

Authors

Marten Szibor

Christina Schenkl

Mario R O Barsottini

Luke Young

Anthony L Moore

Affiliations

Soon will be listed here.

Abstract

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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