scholarly journals Redox Regulation of Calcium Signaling in Cancer Cells by Ascorbic Acid Involving the Mitochondrial Electron Transport Chain

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Grigory G. Martinovich ◽  
Elena N. Golubeva ◽  
Irina V. Martinovich ◽  
Sergey N. Cherenkevich
Keyword(s):  
Ascorbic Acid ◽  
Electron Transport ◽  
Calcium Signaling ◽  
Electron Transport Chain ◽  
Redox Regulation ◽  
Complex Iii ◽  
Antimycin A ◽  
Ros Production ◽  
Mitochondrial Complex ◽  
Transport Chain

Previously, we have reported that ascorbic acid regulates calcium signaling in human larynx carcinoma HEp-2 cells. To evaluate the precise mechanism of Ca2+ release by ascorbic acid, the effects of specific inhibitors of the electron transport chain components on mitochondrial reactive oxygen species (ROS) production and Ca2+ mobilization in HEp-2 cells were investigated. It was revealed that the mitochondrial complex III inhibitor (antimycin A) amplifies ascorbate-induced Ca2+ release from intracellular stores. The mitochondrial complex I inhibitor (rotenone) decreases Ca2+ release from intracellular stores in HEp-2 cells caused by ascorbic acid and antimycin A. In the presence of rotenone, antimycin A stimulates ROS production by mitochondria. Ascorbate-induced Ca2+ release in HEp-2 cells is shown to be unaffected by catalase. The results obtained suggest that Ca2+ release in HEp-2 cells caused by ascorbic acid is associated with induced mitochondrial ROS production. The data obtained are in line with the concept of redox signaling that explains oxidant action by compartmentalization of ROS production and oxidant targets.

Ischemic defects in the electron transport chain increase the production of reactive oxygen species from isolated rat heart mitochondria

2008 ◽  
Vol 294 (2) ◽  
pp. C460-C466 ◽  
Author(s):  
Qun Chen ◽  
Shadi Moghaddas ◽  
Charles L. Hoppel ◽  
Edward J. Lesnefsky
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Electron Transport Chain ◽  
Myocardial Injury ◽  
Complex Iii ◽  
Ischemic Damage ◽  
Ros Production ◽  
Oxygen Species ◽  
Net Production ◽  
Transport Chain

Cardiac ischemia decreases complex III activity, cytochrome c content, and respiration through cytochrome oxidase in subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). The reversible blockade of electron transport with amobarbital during ischemia protects mitochondrial respiration and decreases myocardial injury during reperfusion. These findings support that mitochondrial damage occurs during ischemia and contributes to myocardial injury during reperfusion. The current study addressed whether ischemic damage to the electron transport chain (ETC) increased the net production of reactive oxygen species (ROS) from mitochondria. SSM and IFM were isolated from 6-mo-old Fisher 344 rat hearts following 25 min global ischemia or following 40 min of perfusion alone as controls. H2O2release from SSM and IFM was measured using the amplex red assay. With glutamate as a complex I substrate, the net production of H2O2was increased by 178 ± 14% and 179 ± 17% in SSM and IFM ( n = 9), respectively, following ischemia compared with controls ( n = 8). With succinate as substrate in the presence of rotenone, H2O2increased by 272 ± 22% and 171 ± 21% in SSM and IFM, respectively, after ischemia. Inhibitors of electron transport were used to assess maximal ROS production. Inhibition of complex I with rotenone increased H2O2production by 179 ± 24% and 155 ± 14% in SSM and IFM, respectively, following ischemia. Ischemia also increased the antimycin A-stimulated production of H2O2from complex III. Thus ischemic damage to the ETC increased both the capacity and the net production of H2O2from complex I and complex III and sets the stage for an increase in ROS production during reperfusion as a mechanism of cardiac injury.

scholarly journals Glutathionylated and Fe–S cluster containing hMIA40 (CHCHD4) regulates ROS and mitochondrial complex III and IV activities of the electron transport chain

Redox Biology ◽  
2020 ◽  
Vol 37 ◽  
pp. 101725
Author(s):  
Venkata Ramana Thiriveedi ◽  
Ushodaya Mattam ◽  
Prasad Pattabhi ◽  
Vandana Bisoyi ◽  
Noble Kumar Talari ◽  
...  
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Complex Iii ◽  
Mitochondrial Complex ◽  
Transport Chain

scholarly journals Mitochondrial Electron Transport Chain Complex III Is Required for Antimycin A to Inhibit Autophagy

2011 ◽  
Vol 18 (11) ◽  
pp. 1474-1481 ◽  
Author(s):  
Xiuquan Ma ◽  
Mingzhi Jin ◽  
Yu Cai ◽  
Hongguang Xia ◽  
Kai Long ◽  
...  
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Chain Complex ◽  
Complex Iii ◽  
Antimycin A ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain

scholarly journals The Mitochondrion: A Link Between Hemolysis and Platelet Activation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-39-SCI-39
Author(s):  
Sruti Shiva
Keyword(s):  
Electron Transport ◽  
Platelet Activation ◽  
Electron Transport Chain ◽  
Ex Vivo ◽  
Vascular Occlusion ◽  
Ros Production ◽  
Mitochondrial Complex ◽  
Free Hemoglobin ◽  
Mitochondrial Ros ◽  
Transport Chain

Patients with Sickle Cell Disease (SCD) demonstrate characteristics of chronic hemostatic activation including elevated baseline platelet activation. While it is well established that platelet activation is positively correlated with the magnitude of erythrocytic hemolysis in these patients, the mechanisms linking hemolysis to platelet activation remain unclear. In this study, we investigate the role of the platelet mitochondrion as the molecular link between hemolysis and downstream platelet activation. Using extracellular flux analysis, we demonstrate that platelets isolated from patients with SCD show a distinct alteration in mitochondrial function characterized by a decrease in the activity of the mitochondrial ATP Synthase (electron transport chain Complex V), which leads to enhanced mitochondrial membrane potential and elevated reactive oxygen species (ROS) production by the electron transport chain. Notably, levels of platelet mitochondrial ROS production was significantly correlated with markers of hemolysis (lactate dehydrogenase and plasma free hemoglobin concentration) as well as platelet activation in this cohort. Moreover, the mitochondrial dysfunction observed in platelets from SCD patients was recapitulated by exposing healthy platelets to cell-free hemoglobin ex vivo. Importantly, augmented mitochondrial ROS generation appears to initiate platelet activation, as scavenging of mitochondrial ROS inhibited cell free hemoglobin-induced activation of healthy platelets. Studies in the Berkley (BERK) transgenic murine model of SCD supported ex vivo data demonstrating that hemolysis-induced mitochondrial ROS production stimulates platelet activation. Homozygous BERK mice showed significantly inhibited platelet mitochondrial complex V activity and elevated mitochondrial ROS production, concomitant with enhanced baseline platelet activation compared to hemizygote mice. When subjected to a ferric chloride-induced vascular injury model of thrombosis, BERK homozygous mice showed a significantly shorter time to vascular occlusion due to thrombosis compared to hemizygote mice. Treatment of homozygous BERK mice with the mitochondrial ROS scavenger MitoTEMPO (supplemented in drinking water) significantly increased time to vascular occlusion in the ferric chloride thrombosis model. These ex vivo human platelet data and in vivo studies in murine models demonstrate that hemolysis induces platelet mitochondrial ROS production, which stimulates downstream platelet activation. Ongoing studies are focused on determining the molecular mechanisms by which cell free hemoglobin elicits an inhibition of platelet mitochondrial Complex V and implicate a role for activation of the platelet surface toll like receptor 4 (TLR4). Collectively, these data identify the platelet mitochondrion as an important signaling hub that links hemolysis to platelet activation in SCD patients. The potential of therapeutically modulating platelet mitochondrial ROS production to attenuate hemolysis induced thrombotic activation will be discussed. Disclosures No relevant conflicts of interest to declare.

scholarly journals AB0031 T HELPER 17 CELLS WERE SIGNIFICANTLY DECREASED BY MITOCHONDRIAL ELECTRON TRANSPORT CHAIN COMPLEX INHIBITOR IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1318.2-1318
Author(s):  
H. R. Lee ◽  
S. J. Yoo ◽  
J. Kim ◽  
I. S. Yoo ◽  
C. K. Park ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Electron Transport ◽  
Disease Activity ◽  
Th17 Cells ◽  
Electron Transport Chain ◽  
Chain Complex ◽  
Complex Iii ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain ◽  
Healthy Control

Background:Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RAObjectives:To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors.Methods:Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining.Results:The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1>DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased.Conclusion:The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production.References:[1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9.[2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8.Disclosure of Interests:None declared

scholarly journals Mechanistic Electron Transport Chain Model Explains ROS Production in Different Respiratory Modes

2013 ◽  
Vol 104 (2) ◽  
pp. 304a-305a
Author(s):  
Laura D. Gauthier ◽  
Sonia Cortassa ◽  
Joseph L. Greenstein ◽  
Raimond L. Winslow
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Chain Model ◽  
Ros Production ◽  
Transport Chain

scholarly journals A Chemogenomic Screen in Saccharomyces cerevisiae Uncovers a Primary Role for the Mitochondria in Farnesol Toxicity and Its Regulation by the Pkc1 Pathway

2006 ◽  
Vol 282 (7) ◽  
pp. 4868-4874 ◽  
Author(s):  
Gregory D. Fairn ◽  
Kendra MacDonald ◽  
Christopher R. McMaster
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Electron Transport ◽  
Signaling Pathway ◽  
Electron Transport Chain ◽  
Reactive Oxygen ◽  
Complex Iii ◽  
Oxygen Species ◽  
Transport Chain

The isoprenoid farnesol has been shown to preferentially induce apoptosis in cancerous cells; however, the mode of action of farnesol-induced death is not established. We used chemogenomic profiling using Saccharomyces cerevisiae to probe the core cellular processes targeted by farnesol. This screen revealed 48 genes whose inactivation increased sensitivity to farnesol. The gene set indicated a role for the generation of oxygen radicals by the Rieske iron-sulfur component of complex III of the electron transport chain as a major mediator of farnesol-induced cell death. Consistent with this, loss of mitochondrial DNA, which abolishes electron transport, resulted in robust resistance to farnesol. A genomic interaction map predicted interconnectedness between the Pkc1 signaling pathway and farnesol sensitivity via regulation of the generation of reactive oxygen species. Consistent with this prediction (i) Pkc1, Bck1, and Mkk1 relocalized to the mitochondria upon farnesol addition, (ii) inactivation of the only non-essential and non-redundant member of the Pkc1 signaling pathway, BCK1, resulted in farnesol sensitivity, and (iii) expression of activated alleles of PKC1, BCK1, and MKK1 increased resistance to farnesol and hydrogen peroxide. Sensitivity to farnesol was not affected by the presence of the osmostabilizer sorbitol nor did farnesol affect phosphorylation of the ultimate Pkc1-responsive kinase responsible for controlling the cell wall integrity pathway, Slt2. The data indicate that the generation of reactive oxygen species by the electron transport chain is a primary mechanism by which farnesol kills cells. The Pkc1 signaling pathway regulates farnesol-mediated cell death through management of the generation of reactive oxygen species.

Activity of complex III of the mitochondrial electron transport chain is essential for early heart muscle cell differentiation

2004 ◽  
Vol 18 (11) ◽  
pp. 1300-1302 ◽  
Author(s):  
Dimitry Spitkovsky ◽  
Philipp Sasse ◽  
Eugen Kolossov ◽  
Cornelia Böttinger ◽  
Bernd K. Fleischmann ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Electron Transport ◽  
Muscle Cell ◽  
Heart Muscle ◽  
Electron Transport Chain ◽  
Complex Iii ◽  
Mitochondrial Electron Transport Chain ◽  
Heart Muscle Cell ◽  
Muscle Cell Differentiation ◽  
Transport Chain

scholarly journals Inhibition of Mitochondrial Complex III in Candida Albicans ADH1 Deletion Mutant Attenuates Its Pathogenicity Significantly

2021 ◽  
Author(s):  
Hui Guo ◽  
Yi Shan Zhang ◽  
Yan Jun Song ◽  
Ya Jing Zhao ◽  
Shui Xiu Li ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Alternative Oxidase ◽  
Oxidase Inhibitor ◽  
Complex Iii ◽  
Ros Production ◽  
Mitochondrial Complex ◽  
Aerobic Growth ◽  
Transport Chain ◽  
Atp Generation

Abstract Fermentation and aerobic respiration in mitochondria are coordinately regulated and compensated either when C. albicans grows in vitro or in the hosts, and the creature gain the strong viability. It’s insufficient to influent the growth, reproduction and pathogenicity of C. albicans by inhibiting the electron transport chain (ECT) CI, CII, CIII, CV, or fermentation related gene ADH1. Our study showed that the induction of AA (inhibitor of complex III) rather than SHAM (alternative oxidase inhibitor) abolishes the mitochondrial function completely （96% less ATP generation, 59% reduction in MMP), and increases ROS production significantly in ADH1-deleted mutant ( adh1Δ/ adh1Δ ) that in turn becomes hypersensitive to azole and apoptosis, less viable and more difficult to form hyphae. At the same time, the expression of virulence related genes ALS3 and HWP1 were significantly lower than that of WT under AA induction. Under the induction of AA, the mitochondrial function of WT was slightly damaged and cell apoptosis increased slightly，ROS production and sensitivity of azoles increased significantly, but mycelium formation and the growth of cells were not affected. Under aerobic growth, we observed an ADH1 - dependent mitochondrial effect in C. albicans demonstrated by 64% less ATP generation, 58% reduction in MMP and significant elevations of the ROS and apoptosis in ADH1 -deleted mutant. However, mycelium formation and azole susceptibility are not affected. Our results suggested that ADH1 plus CIII played an important role in antifungal activity by damaging mitochondrial function, inhibiting cell growth and hyphae formation, promoting apoptosis and reducing pathogenicity.

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