Department of Clinical Neurosciences and UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.
CCMAR-Centro de Ciências do Mar, Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal.
Cells. 2021 Jan 25;10(2):233. doi: 10.3390/cells10020233.
Reactive oxygen species (ROS) are produced continuously throughout the cell as products of various redox reactions. Yet these products function as important signal messengers, acting through oxidation of specific target factors. Whilst excess ROS production has the potential to induce oxidative stress, physiological roles of ROS are supported by a spatiotemporal equilibrium between ROS producers and scavengers such as antioxidative enzymes. In the endoplasmic reticulum (ER), hydrogen peroxide (HO), a non-radical ROS, is produced through the process of oxidative folding. Utilisation and dysregulation of HO in particular that generated in the ER, affects not only cellular homeostasis but also the longevity of organisms. ROS dysregulation has been implicated in various pathologies including dementia and other neurodegenerative diseases, sanctioning a field of research that strives to better understand cell-intrinsic ROS production. Here we review the organelle-specific ROS-generating and consuming pathways, providing evidence that the ER is a major contributing source of potentially pathologic ROS.
活性氧（ROS）作为各种氧化还原反应的产物，在细胞内持续产生。然而，这些产物作为重要的信号信使，通过特定靶因子的氧化作用发挥作用。虽然过量的 ROS 产生有可能引起氧化应激，但 ROS 的生理作用是通过 ROS 产生者和清除剂（如抗氧化酶）之间的时空平衡来支持的。在内质网（ER）中，通过氧化折叠过程产生过氧化氢（HO），一种非自由基 ROS。HO 的利用和失调，特别是 ER 中产生的 HO 的利用和失调，不仅影响细胞内稳态，还影响生物体的寿命。ROS 失调与各种病理学有关，包括痴呆和其他神经退行性疾病，这促使人们开展了一个旨在更好地理解细胞内 ROS 产生的研究领域。在这里，我们回顾了细胞器特异性的 ROS 产生和消耗途径，提供了证据表明 ER 是潜在病理性 ROS 的主要来源。
