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.

中文翻译：

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针对人类健康和粮食安全的替代氧化酶 (AOX)、药物和农用化学品目标还是救援机制？

一些最具威胁性的人类疾病是由于线粒体电子传递链 (ETC) 的阻塞。在各种植物、真菌和原核生物中，存在一种自然进化的机制来应对这种对生存能力的威胁，即呼吸链的替代酶绕过 ETC 的阻塞部分。一种这样的酶是替代氧化酶（AOX）。当 AOX 表达时，它使宿主能够在危及生命的条件下生存，或者像寄生虫一样，逃避宿主防御。在脊椎动物中，这种机制在进化过程中已经丢失。然而，我们和其他人已经证明，将 AOX 转移到果蝇和小鼠的基因组中会产生催化作用的 AOX。这意味着 AOX 不仅是对抗人类或农业病原体的有希望的目标，而且还是一种阐明疾病机制的新方法，或者在某些情况下，可能是人类疾病的治疗方法。在这篇综述中，我们强调了 AOX 在其天然宿主中和异位表达时的不同功能，并讨论了由此产生的开发物种特异性 AOX 抑制剂的需求。