The alternative oxidase, AOX, provides a by-pass of the cytochrome segment of the mitochondrial respiratory chain when the chain is unavailable. AOX is absent from mammals, but AOX from Ciona intestinalis is benign when expressed in mice. Although non-protonmotive, so does not contribute directly to ATP production, it has been shown to modify and in some cases rescue phenotypes of respiratory-chain disease models. Here we studied the effect of C. intestinalis AOX on mice engineered to express a disease-equivalent mutant of Uqcrh, encoding the hinge subunit of mitochondrial respiratory complex III, which results in a complex metabolic phenotype beginning at 4–5 weeks, rapidly progressing to lethality within a further 6–7 weeks. AOX expression delayed the onset of this phenotype by several weeks, but provided no long-term benefit. We discuss the significance of this finding in light of the known and hypothesized effects of AOX on metabolism, redox homeostasis, oxidative stress and cell signaling. Although not a panacea, the ability of AOX to mitigate disease onset and progression means it could be useful in treatment.

当线粒体呼吸链不可用时，替代氧化酶 AOX 可以绕过线粒体呼吸链的细胞色素片段。哺乳动物中不存在 AOX，但海鞘中的 AOX在小鼠中表达时是良性的。尽管非质子动力，因此不会直接促进 ATP 的产生，但它已被证明可以改变并在某些情况下挽救呼吸链疾病模型的表型。在这里，我们研究了肠棒状杆菌AOX 对表达 Uqcrh 疾病等效突变体的小鼠的影响，Uqcrh 编码线粒体呼吸复合物 III 的铰链亚基，导致在 4-5 周开始出现复杂的代谢表型，并迅速进展到6-7 周内即可致死。AOX 表达使这种表型的发生延迟了几周，但没有提供长期益处。我们根据 AOX 对代谢、氧化还原稳态、氧化应激和细胞信号传导的已知和假设影响讨论了这一发现的重要性。尽管 AOX 不是万能药，但它能够减轻疾病的发作和进展，这意味着它可以用于治疗。