scholarly journals Short OGA is targeted to the mitochondria and regulates mitochondrial reactive oxygen species level

2021 ◽  
Author(s):  
Patrick Pagesy ◽  
Abdelouhab Bouaboud ◽  
Zhihao Feng ◽  
Philippe Hulin ◽  
Tarik Issad
Keyword(s):  
Splice Variants ◽  
Fluorescent Microscopy ◽  
Cell Fractionation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Post Translational Modification ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Microscopy Imaging ◽  
Mitochondrial Ros

O-GlcNAcylation is a reversible post-translational modification involved the regulation of cytosolic, nuclear and mitochondrial proteins. Only two enzymes, OGT and OGA, control attachment and removal of O-GlcNAc on proteins, respectively. Whereas a variant OGT (mOGT) has been proposed as the main isoform that O-GlcNAcylates proteins in mitochondria, identification of a mitochondrial OGA has not been performed yet. Two splice variants of OGA (short and long isoforms) have been described previously. In this work, using cell fractionation experiments, we show that short-OGA is preferentially recovered in mitochondria-enriched fractions from HEK-293T cells as well as mouse embryonic fibroblasts. Moreover, fluorescent microscopy imaging confirmed that GFP-tagged short-OGA is addressed to mitochondria. In addition, using a BRET-based mitochondrial O-GlcNAcylation biosensor, we show that co-transfection of short-OGA markedly reduced O-GlcNAcylation of the biosensor, whereas long-OGA had no significant effect. Finally, using genetically encoded or chemical fluorescent mitochondrial probes, we showed that short-OGA overexpression increases mitochondrial ROS levels, whereas long-OGA had no significant effect. Together, our work reveals that the short-OGA isoform is targeted to the mitochondria where it regulates ROS homoeostasis.

scholarly journals Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e22453 ◽  
Author(s):  
Aaron C-H. Chen ◽  
Praveen R. Arany ◽  
Ying-Ying Huang ◽  
Elizabeth M. Tomkinson ◽  
Sulbha K. Sharma ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Laser Therapy ◽  
Reactive Oxygen ◽  
Low Level Laser Therapy ◽  
Oxygen Species ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Low Level ◽  
Low Level Laser ◽  
Level Laser

scholarly journals Protein Kinase D Mediates Mitochondrion-to-Nucleus Signaling and Detoxification from Mitochondrial Reactive Oxygen Species

2005 ◽  
Vol 25 (19) ◽  
pp. 8520-8530 ◽  
Author(s):  
Peter Storz ◽  
Heike Döppler ◽  
Alex Toker
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Reactive Oxygen ◽  
Protein Kinase D ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Oxidative Stress ◽  
Cellular Survival ◽  
Mitochondrial Ros

ABSTRACT Efficient elimination of mitochondrial reactive oxygen species (mROS) correlates with increased cellular survival and organism life span. Detoxification of mitochondrial ROS is regulated by induction of the nuclear SOD2 gene, which encodes the manganese-dependent superoxide dismutase (MnSOD). However, the mechanisms by which mitochondrial oxidative stress activates cellular signaling pathways leading to induction of nuclear genes are not known. Here we demonstrate that release of mROS activates a signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-κB transcription factor, leading to induction of SOD2. Conversely, the FOXO3a transcription factor is dispensable for mROS-induced SOD2 induction. PKD-mediated MnSOD expression promotes increased survival of cells upon release of mROS, suggesting that mitochondrion-to-nucleus signaling is necessary for efficient detoxification mechanisms and cellular viability.

scholarly journals Interactions between Cytosolic Phospholipase A2 Activation and Mitochondrial Reactive Oxygen Species Production in the Development of Ventilator-Induced Diaphragm Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xian-Long Zhou ◽  
Xiao-Jun Wei ◽  
Shao-Ping Li ◽  
Rui-Ning Liu ◽  
Ming-Xia Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Phospholipase A2 ◽  
Cytosolic Phospholipase A2 ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Diaphragm Dysfunction ◽  
Cytosolic Phospholipase ◽  
Mitochondrial Ros ◽  
Cpla2 Activation

Cytosolic phospholipase A2 (cPLA2) has been reported to be critical for infection-induced mitochondrial reactive oxygen species (ROS) production and diaphragm dysfunction (DD). In the present study, we aim to investigate whether cPLA2 was involved in ventilator-induced diaphragm dysfunction (VIDD). Our results showed that mechanical ventilation (MV) induced cPLA2 activation in the diaphragm with excessive mitochondrial ROS generation and muscle weakness. Specific inhibition of cPLA2 with CDIBA resulted in decreased mitochondrial ROS levels and improved diaphragm forces. In addition, mitochondria-targeted antioxidant MitoTEMPO attenuated ventilator-induced mitochondrial oxidative stress and downregulated cPLA2 activation in vivo. Both CDIBA and MitoTEMPO were able to attenuate protein degradation, muscle atrophy, and weakness following prolonged MV. Furthermore, laser Doppler imaging showed that MV decreased diaphragm tissue perfusion and induced subsequent hypoxia. An in vitro study also demonstrated a positive association between cPLA2 activation and mitochondrial ROS generation in C2C12 cells cultured under hypoxic condition. Collectively, our study showed that cPLA2 activation positively interacts with mitochondrial ROS generation in the development of VIDD, and ventilator-induced diaphragm hypoxia serves as a possible contributor to this positive feedback loop.

scholarly journals Mitochondrial ROS and radiation induced transformation in mouse embryonic fibroblasts

2009 ◽  
Vol 8 (20) ◽  
pp. 1962-1971 ◽  
Author(s):  
Changbin Du ◽  
Zhen Gao ◽  
Venkatasubbaiah A. Venkatesha ◽  
Amanda L. Kalen ◽  
Leena Chaudhuri ◽  
...  
Keyword(s):  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Mitochondrial Ros ◽  
Radiation Induced

Triterpenoids fromZiziphus jujubainduce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production

2018 ◽  
Vol 9 (7) ◽  
pp. 3895-3905 ◽  
Author(s):  
Minna Shin ◽  
Bo-Mi Lee ◽  
Okwha Kim ◽  
Huynh Nguyen Khanh Tran ◽  
Suhyun Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Apoptotic Cell Death ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Human Cancer Cells ◽  
Mitochondrial Ros ◽  
Species Production

Coumaroyl alphitolic acids induce apoptotic cell death in cancer cellsviamitochondrial ROS production and ER stress.

Sodium Ion Regulates Mitochondrial ROS

2021 ◽  
Vol 11 ◽  
Author(s):  
Editorial Office ROS
Keyword(s):  
Reactive Oxygen Species ◽  
T Cell Activation ◽  
Solid Phase ◽  
3D Visualization ◽  
Reactive Oxygen ◽  
Sodium Ion ◽  
Calcium Stores ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Ros

In addition to the diverse well-known physiological functions and pathophysiological effects of sodium ion (Na⁺), regulation of mitochondrial reactive oxygen species (ROS) by Na⁺ has recently been demonstrated by several studies published in highly influential journals. The findings from these studies, especially the proposed “cytosolic Na⁺‒Na⁺/Ca²⁺ exchanger‒mitochondrial ROS” axis, have greatly broadened our understanding of this most popular element in physiology and disease. REFERENCES Kohlhaas M, Liu T, Knopp A, Zeller T, Ong MF, Bohm M, et al. Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes. Circulation 2010; 121(14):1606-13. doi: https://dx.doi.org/10.1161/CIRCULATIONAHA.109.914911. Dey S, DeMazumder D, Sidor A, Foster DB, O'Rourke B. Mitochondrial ROS drive sudden cardiac death and chronic proteome remodeling in heart failure. Circ Res 2018; 123(3):356-71. doi: https://dx.doi.org/10.1161/CIRCRESAHA.118.312708. Murphy E, Eisner DA. Regulation of intracellular and mitochondrial sodium in health and disease. Circ Res 2009; 104(3):292-303. doi: https://dx.doi.org/10.1161/CIRCRESAHA.108.189050. Adrogue HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med 2007; 356(19):1966-78. doi: https://dx.doi.org/10.1056/NEJMra064486. Hernansanz-Agustin P, Choya-Foces C, Carregal-Romero S, Ramos E, Oliva T, Villa-Pina T, et al. Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Nature 2020; 586(7828):287-91. doi: https://dx.doi.org/10.1038/s41586-020-2551-y. Wolf SG, Mutsafi Y, Dadosh T, Ilani T, Lansky Z, Horowitz B, et al. 3D visualization of mitochondrial solid-phase calcium stores in whole cells. Elife 2017; 6. doi: https://dx.doi.org/10.7554/eLife.29929. Shadel GS, Horvath TL. Mitochondrial ROS signaling in organismal homeostasis. Cell 2015; 163(3):560-9. doi: https://dx.doi.org/10.1016/j.cell.2015.10.001. Oberkampf M, Guillerey C, Mouries J, Rosenbaum P, Fayolle C, Bobard A, et al. Mitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells. Nat Commun 2018; 9(1):2241. doi: https://dx.doi.org/10.1038/s41467-018-04686-8. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 2013; 38(2):225-36. doi: https://dx.doi.org/10.1016/j.immuni.2012.10.020.

Abstract 15983: Increased Mitochondrial Reactive Oxygen Species Lead to Deleterious JNK Signaling and Ischemia-Reperfusion Injury in AMPK-Inactivated Hearts

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Vlad G Zaha ◽  
Dake Qi ◽  
Hui-Young Lee ◽  
Xiaoyue Hu ◽  
Xiaohong Wu ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Myocardial Necrosis ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Jnk Signaling ◽  
Mitochondrial Ros

AMP-activated kinase (AMPK) is a key stress responsive kinase that regulates cellular adaptation to metabolic stress. Inactivation of AMPK in “kinase-dead” (KD) mice increases myocardial damage following ischemia-reperfusion (IR). We have also shown decreased mitochondrial respiration and increased mitochondrial reactive oxygen species (ROS) production and susceptibility to mitochondrial transition pore opening in KD hearts following IR. The aim of this study was to establish the importance of mitochondrial ROS production and downstream deleterious signaling to mediate tissue damage in absence of active AMPK in the heart. Detoxification of mitochondrial ROS requires conversion of hydrogen peroxide to water, therefore, we studied the effect of transgenic expression of mitochondrial catalase (MCAT) in wild type (WT) and KD mice. MCAT prevents mitochondrial hydrogen peroxide production independent of mitochondrial energy production. Myocardial necrosis was assessed in vitro after global ischemia-reperfusion and in vivo after LAD ligation and reperfusion. Mitogen activated protein kinase kinase 4 (MKK4) and downstream c-Jun terminal kinase (JNK) expression and phosphorylation was assessed in vivo. Increased necrosis in KD hearts following mild global ischemia (15 minutes) - reperfusion (10 minutes) in vitro, was prevented by expression of MCAT (WT vs. KD 17.8±4.1 vs. 50±4.1%, p<0.05 and MCAT-WT vs. MCAT-KD 16.9±4.8 vs. 29.3±4.4%, n.s., and factorial p<0.05). Total JNK protein was not increased in WT and KD hearts with or without expression of MCAT. After coronary occlusion in vivo, KD mice showed increased cardiac activation of MKK4/JNK pathway (p<0.05) as well as greater myocardial necrosis (p<0.05). MCAT expression prevented the excessive cardiac JNK activation observed during IR in KD mice in vivo. Inhibition of JNK with SP600125 (10μM) during in vivo IR also resulted in a significant decrease in necrosis in KD hearts (WT vs. KD 9.1±0.7 vs. 28.2±2.9%, p<0.05 and WT vs. KD with SP600125 8.5±0.5 vs. 10.2±1.1%, n.s. and factorial p<0.05, percentage of equivalent area at risk). Thus, AMPK activation during IR prevents excess mitochondrial reactive oxygen production and consequent JNK signaling, thus protecting against myocardial injury.

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