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.

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.

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 AToxoplasmaProlyl Hydroxylase Mediates Oxygen Stress Responses by Regulating Translation Elongation

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Celia Florimond ◽  
Charlotte Cordonnier ◽  
Rahil Taujale ◽  
Hanke van der Wel ◽  
Natarajan Kannan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Synthesis ◽  
Toxoplasma Gondii ◽  
Oxygen Sensing ◽  
Reactive Oxygen ◽  
Protozoan Parasite ◽  
Cellular Responses ◽  
Parasite Growth ◽  
Oxygen Species ◽  
Prolyl Hydroxylases

ABSTRACTAs the protozoan parasiteToxoplasma gondiidisseminates through its host, it responds to environmental changes by altering its gene expression, metabolism, and other processes. Oxygen is one variable environmental factor, and properly adapting to changes in oxygen levels is critical to prevent the accumulation of reactive oxygen species and other cytotoxic factors. Thus, oxygen-sensing proteins are important, and among these, 2-oxoglutarate-dependent prolyl hydroxylases are highly conserved throughout evolution.Toxoplasmaexpresses two such enzymes, TgPHYa, which regulates the SCF-ubiquitin ligase complex, and TgPHYb. To characterize TgPHYb, we created aToxoplasmastrain that conditionally expresses TgPHYb and report that TgPHYb is required for optimal parasite growth under normal growth conditions. However, exposing TgPHYb-depleted parasites to extracellular stress leads to severe decreases in parasite invasion, which is likely due to decreased abundance of parasite adhesins. Adhesin protein abundance is reduced in TgPHYb-depleted parasites as a result of inactivation of the protein synthesis elongation factor eEF2 that is accompanied by decreased rates of translational elongation. In contrast to most other oxygen-sensing proteins that mediate cellular responses to low O2, TgPHYb is specifically required for parasite growth and protein synthesis at high, but not low, O2tensions as well as resistance to reactive oxygen species.In vivo, reduced TgPHYb expression leads to lower parasite burdens in oxygen-rich tissues. Taken together, these data identify TgPHYb as a sensor of high O2levels, in contrast to TgPHYa, which supports the parasite at low O2.IMPORTANCEBecause oxygen plays a key role in the growth of many organisms, cells must know how much oxygen is available. O2-sensing proteins are therefore critical cellular factors, and prolyl hydroxylases are the best-studied type of O2-sensing proteins. In general, prolyl hydroxylases trigger cellular responses to decreased oxygen availability. But, how does a cell react to high levels of oxygen? Using the protozoan parasiteToxoplasma gondii, we discovered a prolyl hydroxylase that allows the parasite to grow at elevated oxygen levels and does so by regulating protein synthesis. Loss of this enzyme also reduces parasite burden in oxygen-rich tissues, indicating that sensing both high and low levels of oxygen impacts the growth and physiology ofToxoplasma.

scholarly journals Excessive Reactive Oxygen Species Inhibit IL-17A+ γδ T Cells and Innate Cellular Responses to Bacterial Lung Infection

2020 ◽  
Vol 32 (13) ◽  
pp. 943-956
Author(s):  
Desiree Anthony ◽  
Angelica Papanicolaou ◽  
Hao Wang ◽  
Huei Jiunn Seow ◽  
Eunice E. To ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Reactive Oxygen ◽  
Γδ T Cells ◽  
Cellular Responses ◽  
Lung Infection ◽  
Oxygen Species

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 Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle

2010 ◽  
Vol 108 (4) ◽  
pp. 780-787 ◽  
Author(s):  
Kent Sahlin ◽  
Irina G. Shabalina ◽  
C. Mikael Mattsson ◽  
Linda Bakkman ◽  
Maria Fernström ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Vastus Lateralis ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Work Intensity ◽  
Isolated Mitochondria ◽  
Mitochondrial Ros

Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24–32 yr) performed ultraendurance exercise (kayaking/running/cycling) with an average work intensity of 55% V̇o2peak for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise, and after 28 h of recovery. The production of H2O2 was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H2O2 production was significantly increased after exercise (73% higher, P = 0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased fourfold and exceeded 1.2 mmol/l during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production ( r = 0.74, P < 0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol group level and glutathione peroxidase activity were elevated after recovery. In conclusion, ultraendurance exercise increases ROS production in isolated mitochondria, but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise.

scholarly journals Mitochondrial Reactive Oxygen Species Mediate GPCR–induced TACE/ADAM17-dependent Transforming Growth Factor-α Shedding

2009 ◽  
Vol 20 (24) ◽  
pp. 5236-5249 ◽  
Author(s):  
Timothy J. Myers ◽  
Leann H. Brennaman ◽  
Mary Stevenson ◽  
Shigeki Higashiyama ◽  
William E. Russell ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Transforming Growth Factor Α ◽  
Egfr Activation ◽  
Mitochondrial Ros ◽  
Factor Α

Epidermal growth factor receptor (EGFR) activation by GPCRs regulates many important biological processes. ADAM metalloprotease activity has been implicated as a key step in transactivation, yet the regulatory mechanisms are not fully understood. Here, we investigate the regulation of transforming growth factor-α (TGF-α) shedding by reactive oxygen species (ROS) through the ATP-dependent activation of the P2Y family of GPCRs. We report that ATP stimulates TGF-α proteolysis with concomitant EGFR activation and that this process requires TACE/ADAM17 activity in both murine fibroblasts and CHO cells. ATP-induced TGF-α shedding required calcium and was independent of Src family kinases and PKC and MAPK signaling. Moreover, ATP-induced TGF-α shedding was completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding was partially inhibited by ROS scavenging. Hydrogen peroxide restored TGF-α shedding after calcium chelation. Importantly, we also found that ATP-induced shedding was independent of the cytoplasmic NADPH oxidase complex. Instead, mitochondrial ROS production increased in response to ATP and mitochondrial oxidative complex activity was required to activate TACE-dependent shedding. These results reveal an essential role for mitochondrial ROS in regulating GPCR-induced growth factor shedding.

Mitochondrial reactive oxygen species contribute to high NaCl-induced activation of the transcription factor TonEBP/OREBP

2006 ◽  
Vol 290 (5) ◽  
pp. F1169-F1176 ◽  
Author(s):  
Xiaoming Zhou ◽  
Joan D. Ferraris ◽  
Maurice B. Burg
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Reactive Oxygen ◽  
Hek293 Cells ◽  
Organic Osmolytes ◽  
Ros Production ◽  
Oxygen Species ◽  
Hypertonic Stress ◽  
Mitochondrial Ros

Hypertonicity activates the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), resulting in increased expression of genes involved in osmoprotective accumulation of organic osmolytes, including glycine betaine, and in increased expression of osmoprotective heat shock proteins. Our previous studies showed that high NaCl increases reactive oxygen species (ROS), which contribute to activation of TonEBP/OREBP. Mitochondria are a major source of ROS. The purpose of the present study was to examine whether mitochondria produce the ROS that contribute to activation of TonEBP/OREBP. We inhibited mitochondrial ROS production in HEK293 cells with rotenone and myxothiazol, which inhibit mitochondrial complexes I and III, respectively. Rotenone (250 nM) and myxothiazol (12 nM) reduce high NaCl-induced ROS over 40%, whereas apocynin (100 μM), an inhibitor of NADPH oxidase, and allopurinol (100 μM), an inhibitor of xanthine oxidase, have no significant effect. Rotenone and myxothiazol reduce high NaCl-induced increases in TonEBP/OREBP transcriptional activity (ORE/TonE reporter assay) and BGT1 (betaine transporter) mRNA abundance ranging from 53 to 69%. They inhibit high NaCl-induced TonEBP/OREBP transactivating activity, but not its nuclear translocation. Release of ATP into the medium on hypertonic stress has been proposed to be a signal that triggers cellular osmotic responses. However, we do not detect release of ATP into the medium or inhibition of high NaCl-induced ORE/TonE reporter activity by an ATPase, apyrase (20 U/ml), indicating that high NaCl-induced activation of TonEBP/OREBP is not mediated by release of ATP. We conclude that high NaCl increases mitochondrial ROS production, which contributes to the activation of TonEBP/OREBP by increasing its transactivating activity.

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