Intracellular Sources of ROS/H₂O₂ in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

• Main Authors: Tasuku Konno, Eduardo Pinho Melo, Joseph E. Chambers, Edward Avezov
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Cells
• Subjects: reactive oxygen species; hydrogen peroxide; endoplasmic reticulum; redox signalling; antioxidants; neurodegeneration
• Online Access: https://www.mdpi.com/2073-4409/10/2/233

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 (H₂O₂), a non-radical ROS, is produced through the process of oxidative folding. Utilisation and dysregulation of H₂O_2,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.