scholarly journals STING, the Endoplasmic Reticulum, and Mitochondria: Is Three a Crowd or a Conversation?

2021 ◽  
Vol 11 ◽  
Author(s):  
Judith A. Smith
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Mitochondrial Dna ◽  
Functional Relationship ◽  
Nuclear Dna ◽  
Oxygen Species ◽  
Dna Sensor ◽  
Intracellular Organelle ◽  
Organelle Communication ◽  
Recognition Receptor

The anti-viral pattern recognition receptor STING and its partnering cytosolic DNA sensor cGAS have been increasingly recognized to respond to self DNA in multiple pathologic settings including cancer and autoimmune disease. Endogenous DNA sources that trigger STING include damaged nuclear DNA in micronuclei and mitochondrial DNA (mtDNA). STING resides in the endoplasmic reticulum (ER), and particularly in the ER-mitochondria associated membranes. This unique location renders STING well poised to respond to intracellular organelle stress. Whereas the pathways linking mtDNA and STING have been addressed recently, the mechanisms governing ER stress and STING interaction remain more opaque. The ER and mitochondria share a close anatomic and functional relationship, with mutual production of, and inter-organelle communication via calcium and reactive oxygen species (ROS). This interdependent relationship has potential to both generate the essential ligands for STING activation and to regulate its activity. Herein, we review the interactions between STING and mitochondria, STING and ER, ER and mitochondria (vis-à-vis calcium and ROS), and the evidence for 3-way communication.

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

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 233
Author(s):  
Tasuku Konno ◽  
Eduardo Pinho Melo ◽  
Joseph E. Chambers ◽  
Edward Avezov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Antioxidative Enzymes ◽  
Redox Reactions ◽  
Ros Production ◽  
Oxygen Species ◽  
Specific Target

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 H2O2, 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.

Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants

2006 ◽  
Vol 38 (11) ◽  
pp. 1261-1268 ◽  
Author(s):  
Raquel Moreno-Loshuertos ◽  
Rebeca Acín-Pérez ◽  
Patricio Fernández-Silva ◽  
Nieves Movilla ◽  
Acisclo Pérez-Martos ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dna ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Dna Variants ◽  
Species Production ◽  
Mitochondrial Dna Variants

scholarly journals Acute apoptosis by cisplatin requires induction of reactive oxygen species but is not associated with damage to nuclear DNA

2006 ◽  
Vol 120 (1) ◽  
pp. 175-180 ◽  
Author(s):  
Maria Berndtsson ◽  
Maria Hägg ◽  
Theocharis Panaretakis ◽  
Aleksandra Mandic Havelka ◽  
Maria C. Shoshan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nuclear Dna ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Selective Activation of Endoplasmic Reticulum Stress by Reactive-Oxygen-Species-Mediated Ochratoxin A-Induced Apoptosis in Tubular Epithelial Cells

2021 ◽  
Vol 22 (20) ◽  
pp. 10951
Author(s):  
Chong-Sun Khoi ◽  
Yu-Wen Lin ◽  
Jia-Huang Chen ◽  
Biing-Hui Liu ◽  
Tzu-Yu Lin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Ochratoxin A ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Oxygen Species ◽  
Food And Feed ◽  
Renal Proximal Tubular Cells ◽  
Induced Apoptosis

Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.

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