Mitochondria are recognized as centrally important to cellular reactive oxygen species (ROS), both as a potential source and due to their substantial antioxidant capacity. While much of the initial ROS formed by mitochondria is superoxide, this is rapidly converted to hydrogen peroxide (H₂O₂) which more readily crosses membranes making H₂O₂ important in both redox signalling mechanisms and conditions of oxidative stress. Here I outline our studies on mitochondrial H₂O₂ metabolism with a focus on some of the challenges and strategies involved with developing an integrated model of mitochondria being intrinsic regulators of H₂O₂. This view of mitochondria as regulators of H₂O₂ goes beyond the simpler contention of them being net producers or consumers. Moreover, the integration of both consumption and production can then be tied to a putative mechanism linking energy sensing at the level of the mitochondrial protonmotive force. This mechanism would provide a means of mitochondria communicating their energetic status the extramitochondrial compartment via local H₂O₂ concentrations. I conclude by explaining how these concepts developed using rodent muscle as a model have high relevance and applicability to comparative studies.

线粒体被认为对细胞活性氧 (ROS) 至关重要，这既是潜在的来源，也是由于其强大的抗氧化能力。虽然线粒体形成的大部分初始 ROS 是超氧化物，但它会迅速转化为过氧化氢 (H ₂ O ₂ )，后者更容易穿过膜，使 H ₂ O ₂在氧化还原信号传导机制和氧化应激条件中都很重要。在这里，我概述了我们对线粒体 H ₂ O ₂代谢的研究，重点是开发作为 H ₂ O ₂内在调节器的线粒体的综合模型所涉及的一些挑战和策略. 这种将线粒体作为 H ₂ O ₂调节剂的观点超出了将它们作为净生产者或消费者的简单论点。此外，消费和生产的整合可以与在线粒体质子动力水平上连接能量感应的推定机制联系起来。这种机制将提供一种线粒体通过局部 H ₂ O ₂浓度向线粒体外隔室传达其能量状态的手段。最后，我解释了使用啮齿动物肌肉作为模型开发的这些概念如何与比较研究具有高度相关性和适用性。