Mitochondrial (‘mild’) uncoupling and ROS production: physiologically relevant or not?

2011 ◽  
Vol 39 (5) ◽  
pp. 1305-1309 ◽  
Author(s):  
Irina G. Shabalina ◽  
Jan Nedergaard
Keyword(s):  
Membrane Potential ◽  
Oxidative Damage ◽  
Uncoupling Protein ◽  
Electron Flow ◽  
Ros Production ◽  
Present Evidence ◽  
Beneficial Effects ◽  
Reverse Electron Flow ◽  
Species Production ◽  
Mild Uncoupling

During the last decade, the possibility that ‘mild’ uncoupling could be protective against oxidative damage by diminishing ROS (reactive oxygen species) production has attracted much interest. In the present paper, we briefly examine the evidence for this possibility. It is only ROS production from succinate under reverse electron-flow conditions that is sensitive to membrane potential fluctuations, and so only this type of ROS production could be affected; however, the conditions under which succinate-supported ROS production is observed include succinate concentrations that are supraphysiological. Any decrease in membrane potential, even ‘mild uncoupling’, must necessarily lead to large increases in respiration, i.e. it must be markedly thermogenic. Mitochondria within cells are normally ATP-producing and thus already have a diminished membrane potential, and treatment of cells, organs or animals with small amounts of artificial uncoupler does not seem to have beneficial effects that are explainable via reduced ROS production. Although it has been suggested that members of the uncoupling protein family (UCP1, UCP2 and UCP3) may mediate a mild uncoupling, present evidence does not unequivocally support such an effect, e.g. the absence of the truly uncoupling protein UCP1 is not associated with increased oxidative damage. Thus present evidence does not support mild uncoupling as a physiologically relevant alleviator of oxidative damage.

Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling

2003 ◽  
Vol 31 (6) ◽  
pp. 1300-1301 ◽  
Author(s):  
S. Miwa ◽  
M.D. Brand
Keyword(s):  
Reactive Oxygen Species ◽  
Membrane Potential ◽  
Complex I ◽  
Electron Flow ◽  
Ros Production ◽  
Oxygen Species ◽  
Inner Membrane ◽  
Reverse Electron Flow ◽  
The Matrix ◽  
Mild Uncoupling

Mitochondria produce ROS (reactive oxygen species) as a by-product of aerobic respiration. Several studies in mammals and birds suggest that the most physiologically relevant ROS production is from complex I following reverse electron flow, and is highly sensitive to membrane potential. A study of Drosophila mitochondria respiring glycerol 3-phosphate revealed that membrane potential-sensitive ROS production from complex I following reverse electron flow was on the matrix side of the inner membrane. A 10 mV decrease in membrane potential was enough to abolish around 70% of the ROS produced by complex I under these conditions. Another important ROS generator in this model, glycerol-3-phosphate dehydrogenase, produced ROS mostly to the cytosolic side; this ROS production was totally insensitive to a small decrease in membrane potential (10 mV). Thus mild uncoupling may be particularly significant for ROS production from complex I on the matrix side of the mitochondrial inner membrane.

scholarly journals Reactive oxygen species production and discontinuous gas exchange in insects

2011 ◽  
Vol 279 (1730) ◽  
pp. 893-901 ◽  
Author(s):  
Leigh Boardman ◽  
John S. Terblanche ◽  
Stefan K. Hetz ◽  
Elrike Marais ◽  
Steven L. Chown
Keyword(s):  
Reactive Oxygen Species ◽  
Gas Exchange ◽  
Oxidative Damage ◽  
Negative Relationship ◽  
Reactive Oxygen ◽  
Organizational Level ◽  
Ros Production ◽  
Oxygen Species ◽  
Time Flow ◽  
Species Production

While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production.

Effect of Single Layer Centrifugation on reactive oxygen species and sperm mitochondrial membrane potential in cooled stallion semen

2017 ◽  
Vol 29 (5) ◽  
pp. 1039 ◽  
Author(s):  
J. M. Morrell ◽  
A. Lagerqvist ◽  
P. Humblot ◽  
A. Johannisson
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Single Layer ◽  
Ros Production ◽  
Oxygen Species ◽  
Species Production

Additional means are needed for evaluating the quality of stallion spermatozoa in semen doses for AI. Mitochondrial membrane potential (ΔΨm) has been linked to fertility in some species, but is rarely used in the evaluation of cooled stallion semen; metabolic activity may be associated with reactive oxygen species production (ROS). In the present study, ΔΨm and ROS production were measured in doses of cooled stallion semen. The effect of colloid centrifugation on these parameters was also investigated. In this case, colloid centrifugation involves centrifuging a sperm sample through a silane-coated silica colloid formulation to retrieve the most robust spermatozoa. High and low ΔΨm in cooled stallion semen varied between stallions and between ejaculates, but was not affected by single-layer centrifugation (SLC). The SLC-selected spermatozoa produced significantly less hydrogen peroxide than controls (P < 0.001), which could explain the increased longevity and retention of fertilising capacity seen in previous studies. For SLC samples, ΔΨm was positively associated with viable spermatozoa that were not producing reactive oxygen species (r = 0.49; P < 0.001) and negatively associated with ROS production (for superoxide: r = –0.4, P < 0.01; for hydrogen peroxide: r = –0.39, P < 0.05). There was no clear association between ΔΨm and ROS production in control samples.

scholarly journals Olive oil-supplemented diet alleviates acute heat stress-induced mitochondrial ROS production in chicken skeletal muscle

2009 ◽  
Vol 297 (3) ◽  
pp. R690-R698 ◽  
Author(s):  
Ahmad Mujahid ◽  
Yukio Akiba ◽  
Masaaki Toyomizu
Keyword(s):  
Skeletal Muscle ◽  
Heat Stress ◽  
Membrane Potential ◽  
Oxidative Damage ◽  
Olive Oil ◽  
Ros Production ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Mitochondrial Ros ◽  
Acute Heat Stress

We have previously shown that avian uncoupling protein (avUCP) is downregulated on exposure to acute heat stress, stimulating mitochondrial reactive oxygen species (ROS) production and oxidative damage. In this study, we investigated whether upregulation of avUCP could attenuate oxidative damage caused by acute heat stress. Broiler chickens ( Gallus gallus) were fed either a control diet or an olive oil-supplemented diet (6.7%), which has been shown to increase the expression of UCP3 in mammals, for 8 days and then exposed either to heat stress (34°C, 12 h) or kept at a thermoneutral temperature (25°C). Skeletal muscle mitochondrial ROS (measured as H2O2) production, avUCP expression, oxidative damage, mitochondrial membrane potential, and oxygen consumption were studied. We confirmed that heat stress increased mitochondrial ROS production and malondialdehyde levels and decreased the amount of avUCP. As expected, feeding birds an olive oil-supplemented diet increased the expression of avUCP in skeletal muscle mitochondria and decreased ROS production and oxidative damage. Studies on mitochondrial function showed that heat stress increased membrane potential in state 4, which was reversed by feeding birds an olive oil-supplemented diet, although no differences in basal proton leak were observed between control and heat-stressed groups. These results show that under heat stress, mitochondrial ROS production and olive oil-induced reduction of ROS production may occur due to changes in respiratory chain activity as well as avUCP expression in skeletal muscle mitochondria.

Protective Effects of Coenzyme Q10 on Developmental Competence of Porcine Early Embryos

2017 ◽  
Vol 23 (4) ◽  
pp. 849-858 ◽  
Author(s):  
Shuang Liang ◽  
Ying Jie Niu ◽  
Kyung-Tae Shin ◽  
Xiang-Shun Cui
Keyword(s):  
Oxidative Damage ◽  
Coenzyme Q10 ◽  
Cellular Proliferation ◽  
Underlying Mechanism ◽  
Developmental Competence ◽  
Hatching Rate ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Species Production ◽  
Parthenogenetic Embryos

AbstractCoenzyme Q10 (Q10) plays an important role in the cellular antioxidant system by protecting the cells from free-radical oxidative damage and apoptosis. In the present study, we have investigated the effect of Q10 on the preimplantation development of porcine parthenogenetic embryos, as well as the underlying mechanism. The results showed that 100 μM was the optimal concentration of Q10, which resulted in significantly increased cleavage and blastocyst formation rates and improvement of blastocyst quality. Q10 improved the blastocyst hatching rate and cellular proliferation rate in hatching blastocysts and increased the expression of hatching-related genes. Furthermore, Q10 not only decreased reactive oxygen species production, DNA damage levels, and apoptosis in the blastocysts from H2O2-induced oxidative injury, but also maintained mitochondrial function. Taken together, these results indicate that Q10 has beneficial effects on the development of porcine parthenogenetic embryos by preventing oxidative damage and apoptosis.

Abstract 1229: Molecular Mechanisms of Angiotensin II-Mediated Mitochondrial Dysfunction: Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Abdulrahman Doughan ◽  
David Harrison ◽  
Sergey Dikalov
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Membrane Potential ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Oxidative Damage ◽  
Nadph Oxidase ◽  
Ros Production ◽  
Ang Ii ◽  
Intact Cells

Mitochondrial (mito) dysfunction is a prominent feature of most cardiovascular diseases including hypertension, diabetes, and heart failure. Angiotensin II (Ang II) is an important stimulus for atherogenesis and hypertension; however, its effects on mito function remain unknown. We hypothesized that Ang II may induce mito oxidative damage that in turn may decrease endothelial nitric oxide (NO • ) and promote vascular oxidative stress. Mitochondria isolated from control and Ang II (200 nM, 4 hours) treated bovine aortic endothelial cells II were investigated. Electron Spin Resonance was used to study the effect of Ang II on mito ROS production, mito respiration, glutathione content and endothelial NO • . Mitochondrial membrane potential was examined using fluorescence microscopy. Endothelial O 2− • formation was quantified using an HPLC-based dihydroethidium assay. Mitochondrial H 2 O 2 and endothelial O 2− • production increased significantly after treatment of endothelial cells with Ang II. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), uric acid (scavenger of peroxynitrite), chelerythrine (PKC inhibitor), N (G)-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor), 5-hydroxydecanoate (5-HD, mitochondrial ATP-sensitive potassium channels inhibitor) or glibenclamide. Depletion of p22phox subunit of NADPH oxidase with siRNA led to significant (P<0.001) reduction in Ang II-mediated mito ROS production. Angiotensin II decreased mito glutathione content, and mito respiratory control ratio. These responses were attenuated by apocynin, 5-HD and glibenclamide. In addition, 5-HD prevented the Ang II-induced decrease in endothelial NO • (73% in Ang II-treated cells and 94% in Ang II plus 5-HD vs. 100% in control; P < 0.05) and mito membrane potential. These events were not associated with activation of caspase-3. Angiotensin II induces mito dysfunction via a pathway that depends on PKC, the NADPH oxidase and formation of peroxynitrite. Furthermore, mito dysfunction in response to Ang II modulates endothelial NO • and O 2− • generation, which may in turn have ramifications for the development of endothelial dysfunction.

Mitochondrial Ca2+-induced K+ influx increases respiration and enhances ROS production while maintaining membrane potential

2007 ◽  
Vol 292 (1) ◽  
pp. C148-C156 ◽  
Author(s):  
André Heinen ◽  
Amadou K. S. Camara ◽  
Mohammed Aldakkak ◽  
Samhita S. Rhodes ◽  
Matthias L. Riess ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Respiration ◽  
Channel Blocker ◽  
Electron Flow ◽  
Ros Generation ◽  
Ros Production ◽  
Guinea Pig Heart ◽  
Isolated Hearts ◽  
Channel Opening ◽  
Charged Membrane

We recently demonstrated a role for altered mitochondrial bioenergetics and reactive oxygen species (ROS) production in mitochondrial Ca2+-sensitive K+ (mtKCa) channel opening-induced preconditioning in isolated hearts. However, the underlying mitochondrial mechanism by which mtKCa channel opening causes ROS production to trigger preconditioning is unknown. We hypothesized that submaximal mitochondrial K+ influx causes ROS production as a result of enhanced electron flow at a fully charged membrane potential (ΔΨm). To test this hypothesis, we measured effects of NS-1619, a putative mtKCa channel opener, and valinomycin, a K+ ionophore, on mitochondrial respiration, ΔΨm, and ROS generation in guinea pig heart mitochondria. NS-1619 (30 μM) increased state 2 and 4 respiration by 5.2 ± 0.9 and 7.3 ± 0.9 nmol O2·min−1·mg protein−1, respectively, with the NADH-linked substrate pyruvate and by 7.5 ± 1.4 and 11.6 ± 2.9 nmol O2·min−1·mg protein−1, respectively, with the FADH2-linked substrate succinate (+ rotenone); these effects were abolished by the mtKCa channel blocker paxilline. ΔΨm was not decreased by 10–30 μM NS-1619 with either substrate, but H2O2 release was increased by 44.8% (65.9 ± 2.7% by 30 μM NS-1619 vs. 21.1 ± 3.8% for time controls) with succinate + rotenone. In contrast, NS-1619 did not increase H2O2 release with pyruvate. Similar results were found for lower concentrations of valinomycin. The increase in ROS production in succinate + rotenone-supported mitochondria resulted from a fully maintained ΔΨm, despite increased respiration, a condition that is capable of allowing increased electron leak. We propose that mild matrix K+ influx during states 2 and 4 increases mitochondrial respiration while maintaining ΔΨm; this allows singlet electron uptake by O2 and ROS generation.

scholarly journals Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

2018 ◽  
Vol 19 (8) ◽  
pp. 2180 ◽  
Author(s):  
María Ariza ◽  
Tamara Forbes-Hernández ◽  
Patricia Reboredo-Rodríguez ◽  
Sadia Afrin ◽  
Massimiliano Gasparrini ◽  
...  
Keyword(s):  
Biological Activity ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
In Vitro Digestion ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Digestion Process ◽  
Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

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