Reactive oxygen species are generated by the respiratory complex II - evidence for lack of contribution of the reverse electron flow in complex I

FEBS Journal ◽  
2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Rafael Moreno-Sánchez ◽  
Luz Hernández-Esquivel ◽  
Nadia A. Rivero-Segura ◽  
Alvaro Marín-Hernández ◽  
Jiri Neuzil ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Complex I ◽  
Electron Flow ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Complex Ii ◽  
Respiratory Complex ◽  
Reverse Electron Flow

scholarly journals A mechanism to prevent production of reactive oxygen species by Escherichia coli respiratory complex I

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Marius Schulte ◽  
Klaudia Frick ◽  
Emmanuel Gnandt ◽  
Sascha Jurkovic ◽  
Sabrina Burschel ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Reactive Oxygen Species ◽  
Complex I ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Respiratory Complex ◽  
Respiratory Complex I

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.

Attenuation of Mitochondrial Respiration by Sevoflurane in Isolated Cardiac Mitochondria Is Mediated in Part by Reactive Oxygen Species

2004 ◽  
Vol 100 (3) ◽  
pp. 498-505 ◽  
Author(s):  
Matthias L. Riess ◽  
Janis T. Eells ◽  
Leo G. Kevin ◽  
Amadou K. S. Camara ◽  
Michele M. Henry ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Electron Transport ◽  
Complex I ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cardiac Mitochondria ◽  
Reactive Oxygen Species Formation ◽  
Complex Ii ◽  
Anesthetic Preconditioning ◽  
Species Formation

Background Anesthetic preconditioning protects against cardiac ischemia/reperfusion injury. Increases in reduced nicotinamide adenine dinucleotide and reactive oxygen species during sevoflurane exposure suggest attenuated mitochondrial electron transport as a trigger of anesthetic preconditioning. The authors investigated the effects of sevoflurane on respiration in isolated cardiac mitochondria. Methods Mitochondria were isolated from fresh guinea pig hearts, and mitochondrial oxygen consumption was measured in the presence of complex I (pyruvate) or complex II (succinate) substrates. The mitochondria were exposed to 0, 0.13, 0.39, 1.3, or 3.9 mM sevoflurane. State 3 respiration was determined after adenosine diphosphate addition. The reactive oxygen species scavengers manganese(III) tetrakis (4-benzoic acid) porphyrin chloride and N-tert-Butyl-a-(2-sulfophenyl)nitrone sodium (10 microM each), or the K(ATP) channel blockers glibenclamide (2 microM) or 5-hydroxydecanoate (300 microM), were given alone or before 1.3 mM sevoflurane. Results Sevoflurane attenuated respiration for both complex I and complex II substrates, depending on the dose. Glibenclamide and 5-hydroxydecanoate had no effect on this attenuation. Both scavengers, however, abolished the sevoflurane-induced attenuation for complex I substrates, but not for complex II substrates. Conclusion The findings suggest that sevoflurane-induced attenuation of complex I is mediated by reactive oxygen species, whereas attenuation of other respiratory complexes is mediated by a different mechanism. The opening of mitochondrial K(ATP) channels by sevoflurane does not seem to be involved in this effect. Thus, reactive oxygen species formation may not only result from attenuated electron transport by sevoflurane, but it may also contribute to complex I attenuation, possibly leading to a positive feedback and amplification of sevoflurane-induced reactive oxygen species formation in triggering anesthetic preconditioning.

scholarly journals Investigating the function of [2Fe–2S] cluster N1a, the off-pathway cluster in complex I, by manipulating its reduction potential

2013 ◽  
Vol 456 (1) ◽  
pp. 139-146 ◽  
Author(s):  
James A. Birrell ◽  
Klaudia Morina ◽  
Hannah R. Bridges ◽  
Thorsten Friedrich ◽  
Judy Hirst
Keyword(s):  
Reactive Oxygen Species ◽  
Complex I ◽  
Reactive Oxygen Species Production ◽  
Reduction Potential ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Respiratory Complex ◽  
Respiratory Complex I ◽  
Species Production

Two residues that determine the potential of cluster N1a in respiratory complex I were identified, and their effects on its flavin-site reactions were determined. Reduction of cluster N1a by NADH does not affect reactive oxygen species production by the flavin.

scholarly journals Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation–reduction state

2002 ◽  
Vol 368 (2) ◽  
pp. 545-553 ◽  
Author(s):  
Yulia KUSHNAREVA ◽  
Anne N. MURPHY ◽  
Alexander ANDREYEV
Keyword(s):  
Reactive Oxygen Species ◽  
Cytochrome C ◽  
Complex I ◽  
Electron Flow ◽  
Reactive Oxygen ◽  
Complex Iii ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Reduced State

Several lines of evidence indicate that mitochondrial reactive oxygen species (ROS) generation is the major source of oxidative stress in the cell. It has been shown that ROS production accompanies cytochrome c release in different apoptotic paradigms, but the site(s) of ROS production remain obscure. In the current study, we demonstrate that loss of cytochrome c by mitochondria oxidizing NAD+-linked substrates results in a dramatic increase of ROS production and respiratory inhibition. This increased ROS production can be mimicked by rotenone, a complex I inhibitor, as well as other chemical inhibitors of electron flow that act further downstream in the electron transport chain. The effects of cytochrome c depletion from mitoplasts on ROS production and respiration are reversible upon addition of exogenous cytochrome c. Thus in these models of mitochondrial injury, a primary site of ROS generation in both brain and heart mitochondria is proximal to the rotenone inhibitory site, rather than in complex III. ROS production at complex I is critically dependent upon a highly reduced state of the mitochondrial NAD(P)+ pool and is achieved upon nearly complete inhibition of the respiratory chain. Redox clamp experiments using the acetoacetate/d-β-hydroxybutyrate couple in the presence of a maximally inhibitory rotenone concentration suggest that the site is approx. 50mV more electronegative than the NADH/NAD+ couple. In the absence of inhibitors, this highly reduced state of mitochondria can be induced by reverse electron flow from succinate to NAD+, accounting for profound ROS production in the presence of succinate. These results lead us to propose a model of thermodynamic control of mitochondrial ROS production which suggests that the ROS-generating site of complex I is the Fe—S centre N-1a.

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