scholarly journals SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a Guardian of Genomic DNA

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Eri Inoue ◽  
Keizo Tano ◽  
Hanako Yoshii ◽  
Jun Nakamura ◽  
Shusuke Tada ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Genomic Dna ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Intermembrane Space ◽  
Mitochondrial Superoxide Dismutase ◽  
Dt40 Cells ◽  
Cell Lethality ◽  
Normal Cellular Metabolism

Reactive oxygen species (ROSs) are produced during normal cellular metabolism, particularly by respiration in mitochondria, and these ROSs are considered to cause oxidative damage to macromolecules, including DNA. In our previous paper, we found no indication that depletion of mitochondrial superoxide dismutase, SOD2, resulted in an increase in DNA damage. In this paper, we examined SOD1, which is distributed in the cytoplasm, nucleus, and mitochondrial intermembrane space. We generated conditionalSOD1knockout cells from chicken DT40 cells and analyzed their phenotypes. The results revealed that SOD1 was essential for viability and that depletion of SOD1, especially nuclear SOD1, increased sister chromatid exchange (SCE) frequency, suggesting that superoxide is generated in or near the nucleus and that nuclear SOD1 functions as a guardian of the genome. Furthermore, we found that ascorbic acid could offset the defects caused by SOD1 depletion, including cell lethality and increases in SCE frequency and apurinic/apyrimidinic sites.

Apoptosis: bombarding the mitochondria

2003 ◽  
Vol 39 ◽  
pp. 41-51 ◽  
Author(s):  
Philippe Parone ◽  
Muriel Priault ◽  
Dominic James ◽  
Steven F Nothwehr ◽  
Jean-Claude Martinou
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Membrane ◽  
Family Members ◽  
Reactive Oxygen ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Outer Mitochondrial Membrane ◽  
Caspase Activation ◽  
Mitochondrial Intermembrane Space ◽  
Death Signals

Mitochondria play a central role in apoptosis triggered by many stimuli. They integrate death signals through Bcl-2 family members and co-ordinate caspase activation through the release of apoptogenic factors that are normally sequestered in the mitochondrial intermembrane space. The release of these proteins is the result of the outer mitochondrial membrane becoming permeable. In addition, mitochondria can initiate apoptosis through the production of reactive oxygen species.

scholarly journals SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer

2019 ◽  
Vol 116 (47) ◽  
pp. 23534-23541 ◽  
Author(s):  
Chenxia He ◽  
Jeanne M. Danes ◽  
Peter C. Hart ◽  
Yueming Zhu ◽  
Yunping Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Breast Cancer Cells ◽  
Mitochondrial Pathway ◽  
Cell Reprogramming ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Superoxide ◽  
Poor Outcomes ◽  
Mitochondrial Superoxide Dismutase

Mitochondrial superoxide dismutase (SOD2) suppresses tumor initiation but promotes invasion and dissemination of tumor cells at later stages of the disease. The mechanism of this functional switch remains poorly defined. Our results indicate that as SOD2 expression increases acetylation of lysine 68 ensues. Acetylated SOD2 promotes hypoxic signaling via increased mitochondrial reactive oxygen species (mtROS). mtROS, in turn, stabilize hypoxia-induced factor 2α (HIF2α), a transcription factor upstream of “stemness” genes such as Oct4, Sox2, and Nanog. In this sense, our findings indicate that SOD2K68Ac and mtROS are linked to stemness reprogramming in breast cancer cells via HIF2α signaling. Based on these findings we propose that, as tumors evolve, the accumulation of SOD2K68Ac turns on a mitochondrial pathway to stemness that depends on HIF2α and may be relevant for the progression of breast cancer toward poor outcomes.

scholarly journals Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling

2013 ◽  
Vol 456 (3) ◽  
pp. 337-346 ◽  
Author(s):  
Simran S. Sabharwal ◽  
Gregory B. Waypa ◽  
Jeremy D. Marks ◽  
Paul T. Schumacker
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Cellular Responses ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Mitochondrial Intermembrane Space ◽  
Ros Reactive Oxygen Species

This study demonstrates that peroxiredoxin-5 expression in the mitochondrial intermembrane space can scavenge mitochondrial ROS (reactive oxygen species) signals, thereby inhibiting hypoxia-induced cellular responses.

Oxygen-dependent activation of Cu,Zn-superoxide dismutase-1

Metallomics ◽  
2017 ◽  
Vol 9 (8) ◽  
pp. 1047-1059 ◽  
Author(s):  
Morgan M. Fetherolf ◽  
Stefanie D. Boyd ◽  
Duane D. Winkler ◽  
Dennis R. Winge
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Reactive Oxygen ◽  
Intermembrane Space ◽  
Oxygen Species ◽  
Superoxide Dismutase 1 ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc ◽  
Mitochondrial Intermembrane Space

Copper zinc superoxide dismutase (Sod1) is a critical enzyme in limiting reactive oxygen species in both the cytosol and the mitochondrial intermembrane space.

scholarly journals PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Takahito Moriwaki ◽  
Akari Yoshimura ◽  
Yuki Tamari ◽  
Hiroyuki Sasanuma ◽  
Shunichi Takeda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Intracellular Signaling ◽  
Reactive Oxygen ◽  
Fine Tuning ◽  
Oxygen Species ◽  
Ros Homeostasis ◽  
Intracellular Ros ◽  
Chromosomal Breaks ◽  
Dt40 Cells

Abstract Background Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study. Results The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS. Conclusions PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.

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