Department of Biological Sciences, University of Manitoba Winnipeg, MB R3T 2N2, Canada.
Comp Biochem Physiol B Biochem Mol Biol. 2021 Oct-Dec;256:110614. doi: 10.1016/j.cbpb.2021.110614. Epub 2021 May 7.
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 (HO) which more readily crosses membranes making HO important in both redox signalling mechanisms and conditions of oxidative stress. Here I outline our studies on mitochondrial HO metabolism with a focus on some of the challenges and strategies involved with developing an integrated model of mitochondria being intrinsic regulators of HO. This view of mitochondria as regulators of HO 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 HO concentrations. I conclude by explaining how these concepts developed using rodent muscle as a model have high relevance and applicability to comparative studies.
线粒体被认为是细胞活性氧（ROS）的核心，既是潜在的来源，也是因为其具有大量的抗氧化能力。虽然线粒体最初形成的大部分 ROS 是超氧化物，但它很快就会转化为过氧化氢（HO），后者更容易穿过膜，因此在氧化还原信号机制和氧化应激条件下，HO 都很重要。在这里，我概述了我们关于线粒体 HO 代谢的研究，重点介绍了开发 HO 作为线粒体固有调节剂的综合模型所涉及的一些挑战和策略。这种将线粒体视为 HO 调节剂的观点超越了它们仅仅是净生产者或消费者的简单观点。此外，消耗和生产的整合可以与一种假设的机制联系起来，这种机制将在线粒体质子动力势水平上的能量感应联系起来。这种机制将提供一种通过局部 HO 浓度将线粒体的能量状态传递到胞外隔室的方式。最后，我解释了如何使用啮齿动物肌肉作为模型来发展这些概念，这些概念对于比较研究具有很高的相关性和适用性。
