College of Health Sciences, The University of Memphis, Memphis, TN 38152, USA
Calico Life Sciences LLC, South San Francisco, CA 94080, USA.
J Exp Biol. 2021 Mar 11;224(Pt 5):jeb221606. doi: 10.1242/jeb.221606.
Physiologists often assume that mitochondria are the main producers of reactive oxygen species (ROS) in cells. Consequently, in biomedicine, mitochondria are considered as important targets for therapeutic treatments, and in evolutionary biology, they are considered as mediators of life-history tradeoffs. Surprisingly, data supporting such an assumption are lacking, at least partially due to the technical difficulties in accurately measuring the level of ROS produced by different subcellular compartments in intact cells. In this Commentary, we first review three potential reasons underlying the misassumption of mitochondrial dominance in the production of cellular ROS. We then introduce some other major sites/enzymes responsible for cellular ROS production. With the use of a recently developed cell-based assay, we further discuss the contribution of mitochondria to the total rate of ROS release in cell lines and primary cells of different species. In these cells, the contribution of mitochondria varies between cell types but mitochondria are never the main source of cellular ROS. This indicates that although mitochondria are one of the significant sources of cellular ROS, they are not necessarily the main contributor under normal conditions. Intriguingly, similar findings were also observed in cells under a variety of stressors, life-history strategies and pathological stages, in which the rates of cellular ROS production were significantly enhanced. Finally, we make recommendations for designing future studies. We hope this paper will encourage investigators to carefully consider non-mitochondrial sources of cellular ROS in their study systems or models.
生理学家通常假设线粒体是细胞中活性氧（ROS）的主要产生者。因此，在线粒体医学中，它们被认为是治疗靶点的重要目标，而在进化生物学中，它们被认为是寿命权衡的中介。令人惊讶的是，支持这种假设的数据缺乏，至少部分原因是在完整细胞中准确测量不同亚细胞区室产生的 ROS 水平存在技术困难。在这篇评论中，我们首先回顾了线粒体在细胞 ROS 产生中占据主导地位的错误假设的三个潜在原因。然后，我们介绍了其他一些主要的负责细胞 ROS 产生的部位/酶。我们使用最近开发的基于细胞的测定法，进一步讨论了线粒体对不同物种的细胞系和原代细胞中 ROS 总释放率的贡献。在这些细胞中，线粒体的贡献在细胞类型之间有所不同，但线粒体绝不是细胞 ROS 的主要来源。这表明，尽管线粒体是细胞 ROS 的重要来源之一，但在正常情况下，它们不一定是主要来源。有趣的是，在各种应激源、寿命策略和病理阶段下的细胞中也观察到了类似的发现，其中细胞 ROS 产生的速率显著增强。最后，我们对未来研究提出了建议。我们希望本文将鼓励研究人员在他们的研究系统或模型中仔细考虑细胞 ROS 的非线粒体来源。
