scholarly journals Control of mitochondrial superoxide production by reverse electron transport at complex I

2018 ◽  
Vol 293 (25) ◽  
pp. 9869-9879 ◽  
Author(s):  
Ellen L. Robb ◽  
Andrew R. Hall ◽  
Tracy A. Prime ◽  
Simon Eaton ◽  
Marten Szibor ◽  
...  
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Superoxide Production ◽  
Mitochondrial Superoxide ◽  
Reverse Electron Transport

scholarly journals Correction: Control of mitochondrial superoxide production by reverse electron transport at complex I.

2019 ◽  
Vol 294 (19) ◽  
pp. 7966-7966
Author(s):  
Ellen L. Robb ◽  
Andrew R. Hall ◽  
Tracy A. Prime ◽  
Simon Eaton ◽  
Marten Szibor ◽  
...  
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Superoxide Production ◽  
Mitochondrial Superoxide ◽  
Reverse Electron Transport

scholarly journals Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane

2004 ◽  
Vol 382 (2) ◽  
pp. 511-517 ◽  
Author(s):  
Adrian J. LAMBERT ◽  
Martin D. BRAND
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Complex I ◽  
Superoxide Production ◽  
Ph Gradient ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Protonmotive Force ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Reverse Electron Transport

The relationship between protonmotive force and superoxide production by mitochondria is poorly understood. To address this issue, the rate of superoxide production from complex I of rat skeletal muscle mitochondria incubated under a variety of conditions was assessed. By far, the largest rate of superoxide production was from mitochondria respiring on succinate; this rate was almost abolished by rotenone or piericidin, indicating that superoxide production from complex I is large under conditions of reverse electron transport. The high rate of superoxide production by complex I could also be abolished by uncoupler, confirming that superoxide production is sensitive to protonmotive force. It was inhibited by nigericin, suggesting that it is more dependent on the pH gradient across the mitochondrial inner membrane than on the membrane potential. These effects were examined in detail, leading to the conclusions that the effect of protonmotive force was mostly direct, and not indirect through changes in the redox state of the ubiquinone pool, and that the production of superoxide by complex I during reverse electron transport was at least 3-fold more sensitive to the pH gradient than to the membrane potential.

scholarly journals Mitochondrial Respiratory Chain Inhibitors Involved in ROS Production Induced by Acute High Concentrations of Iodide and the Effects of SOD as a Protective Factor

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Lingyan Wang ◽  
Qi Duan ◽  
Tingting Wang ◽  
Mohamed Ahmed ◽  
Na Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Respiratory Chain ◽  
Complex I ◽  
Mitochondrial Respiratory Chain ◽  
Superoxide Production ◽  
Mitochondrial Superoxide ◽  
Ldh Release ◽  
Relative Cell Viability ◽  
Mitochondrial Respiratory

A major source of reactive oxygen species (ROS) generation is the mitochondria. By using flow cytometry of the mitochondrial fluorescent probe, MitoSOX Red, western blot of mitochondrial ROS scavenger Peroxiredoxin (Prx) 3 and fluorescence immunostaining, ELISA of cleaved caspases 3 and 9, and TUNEL staining, we demonstrated that exposure to 100 μM KI for 2 hours significantly increased mitochondrial superoxide production and Prx 3 protein expression with increased expressions of cleaved caspases 3 and 9. Besides, we indicated that superoxide dismutase (SOD) at 1000 unit/mL attenuated the increase in mitochondrial superoxide production, Prx 3 protein expression, and lactate dehydrogenase (LDH) release and improved the relative cell viability at 100 μM KI exposure. However, SOD inhibitor diethyldithiocarbamic acid (DETC) (2 mM), Rotenone (0.5 μM), a mitochondrial complex I inhibitor, and Antimycin A (10 μM), a complex III inhibitor, caused an increase in mitochondrial superoxide production, Prx 3 protein expression, and LDH release and decreased the relative cell viability. We conclude that the inhibitors of mitochondrial respiratory chain complex I or III may be involved in oxidative stress caused by elevated concentrations of iodide, and SOD demonstrates its protective effect on the Fischer rat thyroid cell line (FRTL) cells.

scholarly journals Complex effects of pH on ROS from mitochondrial complex II driven complex I reverse electron transport challenge its role in tissue reperfusion injury

2020 ◽  
Author(s):  
Alexander S. Milliken ◽  
Chaitanya A. Kulkarni ◽  
Paul S. Brookes
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Ischemia Reperfusion ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Effects Of Ph ◽  
Cellular Necrosis ◽  
Reverse Electron Transport ◽  
The Impact

ABSTRACTGeneration of mitochondrial reactive oxygen species (ROS) is an important process in triggering cellular necrosis and tissue infarction during ischemia-reperfusion (IR) injury. Ischemia results in accumulation of the metabolite succinate. Rapid oxidation of this succinate by mitochondrial complex II (Cx-II) during reperfusion reduces the co-enzyme Q (Co-Q) pool, thereby driving electrons backward into complex-I (Cx-I), a process known as reverse electron transport (RET), which is thought to be a major source of ROS. During ischemia, enhanced glycolysis results in an acidic cellular pH at the onset of reperfusion. While the process of RET within Cx-I is known to be enhanced by a high mitochondrial trans-membrane ΔpH, the impact of pH itself on the integrated process of Cx-II to Cx-I RET has not been fully studied. Using isolated mitochondria under conditions which mimic the onset of reperfusion (i.e., high [ADP]). We show that mitochondrial respiration (state 2 and state 3) as well as isolated Cx-II activity are impaired at acidic pH, whereas the overall generation of ROS by Cx-II to Cx-I RET was insensitive to pH. Together these data indicate that the acceleration of Cx-I RET ROS by ΔpH appears to be cancelled out by the impact of pH on the source of electrons, i.e. Cx-II. Implications for the role of Cx-II to Cx-I RET derived ROS in IR injury are discussed.

Mitochondrial superoxide and aging: uncoupling-protein activity and superoxide production

2004 ◽  
Vol 71 ◽  
pp. 203-213 ◽  
Author(s):  
Martin D. Brand ◽  
Julie A. Buckingham ◽  
Telma C. Esteves ◽  
Katherine Green ◽  
Adrian J. Lambert ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Electron Transport ◽  
Complex I ◽  
Uncoupling Protein ◽  
Proton Motive Force ◽  
Motive Force ◽  
Superoxide Production ◽  
Lipid Peroxidation Product ◽  
Mild Uncoupling ◽  
Reversed Electron Transport

Mitochondria are a major source of superoxide, formed by the one-electron reduction of oxygen during electron transport. Superoxide initiates oxidative damage to phospholipids, proteins and nucleic acids. This damage may be a major cause of degenerative disease and aging. In isolated mitochondria, superoxide production on the matrix side of the membrane is particularly high during reversed electron transport to complex I driven by oxidation of succinate or glycerol 3-phosphate. Reversed electron transport and superoxide production from complex I are very sensitive to proton motive force, and can be strongly decreased by mild uncoupling of oxidative phosphorylation. Both matrix superoxide and the lipid peroxidation product 4-hydroxy-trans-2-nonenal can activate uncoupling through endogenous UCPs (uncoupling proteins). We suggest that superoxide releases iron from aconitase, leading to a cascade of lipid peroxidation and the release of molecules such as hydroxy-nonenal that covalently modify and activate the proton conductance of UCPs and other proteins. A function of the UCPs may be to cause mild uncoupling in response to matrix superoxide and other oxidants, leading to lowered proton motive force and decreased superoxide production. This simple feedback loop would constitute a self-limiting cycle to protect against excessive superoxide production, leading to protection against aging, but at the cost of a small elevation of respiration and basal metabolic rate.

Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation

2006 ◽  
Vol 290 (3) ◽  
pp. C844-C851 ◽  
Author(s):  
Ethan J. Anderson ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Basal Respiration ◽  
Superoxide Production ◽  
Complex Iii ◽  
Type I ◽  
Type Ii ◽  
Mitochondrial Content ◽  
Mitochondrial Superoxide

Mitochondrial dysfunction is implicated in a number of skeletal muscle pathologies, most notably aging-induced atrophy and loss of type II myofibers. Although oxygen-derived free radicals are thought to be a primary cause of mitochondrial dysfunction, the underlying factors governing mitochondrial superoxide production in different skeletal myofiber types is unknown. Using a novel in situ approach to measure H2O2 production (indicator of superoxide formation) in permeabilized rat skeletal muscle fiber bundles, we found that mitochondrial free radical leak (H2O2 produced/O2 consumed) is two- to threefold higher ( P < 0.05) in white (WG, primarily type IIB fibers) than in red (RG, type IIA) gastrocnemius or soleus (type I) myofibers during basal respiration supported by complex I (pyruvate + malate) or complex II (succinate) substrates. In the presence of respiratory inhibitors, maximal rates of superoxide produced at both complex I and complex III are markedly higher in RG and WG than in soleus muscle despite ∼50% less mitochondrial content in WG myofibers. Duplicate experiments conducted with ±exogenous superoxide dismutase revealed striking differences in the topology and/or dismutation of superoxide in WG vs. soleus and RG muscle. When normalized for mitochondrial content, overall H2O2 scavenging capacity is lower in RG and WG fibers, whereas glutathione peroxidase activity, which is largely responsible for H2O2 removal in mitochondria, is similar in all three muscle types. These findings suggest that type II myofibers, particularly type IIB, possess unique properties that potentiate mitochondrial superoxide production and/or release, providing a potential mechanism for the heterogeneous development of mitochondrial dysfunction in skeletal muscle.

scholarly journals Mitochondrial superoxide and coenzyme Q in insulin-deficient rats: increased electron leak

2011 ◽  
Vol 301 (6) ◽  
pp. R1616-R1624 ◽  
Author(s):  
Judith A. Herlein ◽  
Brian D. Fink ◽  
Dorlyne M. Henry ◽  
Mark A. Yorek ◽  
Lynn M. Teesch ◽  
...  
Keyword(s):  
Weight Loss ◽  
Electron Transport ◽  
Coenzyme Q ◽  
Tca Cycle ◽  
Diabetic Rats ◽  
Superoxide Production ◽  
Ros Production ◽  
Mitochondrial Superoxide ◽  
Respiratory Parameters

Mitochondrial superoxide is important in the pathogeneses of diabetes and its complications. However, there is uncertainty regarding the intrinsic propensity of mitochondria to generate this radical. Studies to date suggest that superoxide production by mitochondria of insulin-sensitive target tissues of insulin-deficient rodents is reduced or unchanged. Moreover, little is known of the role of the Coenzyme Q (CoQ), whose semiquinone form reacts with molecular oxygen to generate superoxide. We measured reactive oxygen species (ROS) production, respiratory parameters, and CoQ content in mitochondria from gastrocnemius muscle of control and streptozotocin (STZ)-diabetic rats. CoQ content did not differ between mitochondria isolated from vehicle- or STZ-treated animals. CoQ also was unaffected by weight loss in the absence of diabetes (induced by caloric restriction). Under state 4 or state 3 conditions, both respiration and ROS release were reduced in diabetic mitochondria fueled with succinate, glutamate plus malate, or with all three substrates (continuous TCA cycle). However, H2O2 and directly measured superoxide production were substantially increased in gastrocnemius mitochondria of diabetic rats when expressed per unit oxygen consumed. On the basis of substrate and inhibitor effects, the mechanism involved multiple electron transport sites. More limited results using heart mitochondria were similar. ROS per unit respiration was greater in muscle mitochondria from diabetic compared with control rats during state 3, as well as state 4, while the reduction in ROS per unit respiration on transition to state 3 was less for diabetic mitochondria. In summary, ROS production is, in fact, increased in mitochondria from insulin-deficient muscle when considered relative to electron transport. This is evident on multiple energy substrates and in different respiratory states. CoQ is not reduced in diabetic mitochondria or with weight loss due to food restriction. The implications of these findings are discussed.

Sign in / Sign up

Export Citation Format

Share Document