scholarly journals Complex I and cytochrome c are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria

2011 ◽  
Vol 1807 (12) ◽  
pp. 1562-1572 ◽  
Author(s):  
Ricardo Lagoa ◽  
Ilaria Graziani ◽  
Carmen Lopez-Sanchez ◽  
Virginio Garcia-Martinez ◽  
Carlos Gutierrez-Merino
Keyword(s):  
Hydrogen Peroxide ◽  
Cytochrome C ◽  
Complex I ◽  
Molecular Targets ◽  
Hydrogen Peroxide Production

scholarly journals Complex I-Associated Hydrogen Peroxide Production Is Decreased and Electron Transport Chain Enzyme Activities Are Altered in n-3 Enriched fat-1 Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12696 ◽  
Author(s):  
Kevork Hagopian ◽  
Kristina L. Weber ◽  
Darren T. Hwee ◽  
Alison L. Van Eenennaam ◽  
Guillermo López-Lluch ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Electron Transport ◽  
Enzyme Activities ◽  
Complex I ◽  
Electron Transport Chain ◽  
Hydrogen Peroxide Production ◽  
Transport Chain

scholarly journals Identifying Site-specific Superoxide and Hydrogen Peroxide Production Rates from the Mitochondrial Electron Transport System Using a Computational Strategy

2021 ◽  
Author(s):  
Quynh V Duong ◽  
Yan Levitsky ◽  
Maria J Dessinger ◽  
Jason Nolan Bazil
Keyword(s):  
Hydrogen Peroxide ◽  
Electron Transport ◽  
Complex I ◽  
Cellular Damage ◽  
Ros Production ◽  
Hydrogen Peroxide Production ◽  
Pathological Conditions ◽  
Redox Sites ◽  
Mitochondrial Ros ◽  
Ros Homeostasis

Mitochondrial reactive oxygen species (ROS) play important roles in cellular signaling; however, certain pathological conditions such as ischemia/reperfusion (I/R) injury disrupt ROS homeostasis and contribute to cell death. A major impediment to developing therapeutic measures against oxidative stress induced cellular damage is the lack of a quantitative framework to identify the specific sources and regulatory mechanisms of mitochondrial ROS production. We developed a thermodynamically consistent, mass-and-charge balanced, kinetic model of mitochondrial ROS homeostasis focused on redox sites of electron transport chain complexes I, II, and III. The model was calibrated and validated using comprehensive data sets relevant to ROS homeostasis. The model predicts that complex I ROS production dominates other sources under conditions favoring a high membrane potential with elevated NADH and QH2 levels. In general, complex I contributes to significant levels of ROS production under pathological conditions, while complexes II and III are responsible for basal levels of ROS production, especially when QH2 levels are elevated. The model also reveals that hydrogen peroxide production by complex I underlies the non-linear relationship between ROS emission and O2 at low O2 concentrations. Lastly, the model highlights the need to quantify scavenging system activity under different conditions to establish a complete picture of mitochondrial ROS homeostasis. In summary, we describe the individual contributions of the ETS complex redox sites to total ROS emission in mitochondria respiring under various combinations of NADH- and Q-linked respiratory fuels under varying work rates.

scholarly journals Identifying Site-specific Superoxide and Hydrogen Peroxide Production Rates from the Mitochondrial Electron Transport System Using a Computational Strategy

Function ◽  
2021 ◽  
Author(s):  
Quynh V Duong ◽  
Yan Levitsky ◽  
Maria J Dessinger ◽  
Jasiel O Strubbe-Rivera ◽  
Jason N Bazil
Keyword(s):  
Hydrogen Peroxide ◽  
Electron Transport ◽  
Complex I ◽  
Cellular Damage ◽  
Ros Production ◽  
Hydrogen Peroxide Production ◽  
Pathological Conditions ◽  
Redox Sites ◽  
Mitochondrial Ros ◽  
Ros Homeostasis

Abstract Mitochondrial reactive oxygen species (ROS) play important roles in cellular signaling; however, certain pathological conditions such as ischemia/reperfusion (I/R) injury disrupt ROS homeostasis and contribute to cell death. A major impediment to developing therapeutic measures against oxidative stress induced cellular damage is the lack of a quantitative framework to identify the specific sources and regulatory mechanisms of mitochondrial ROS production. We developed a thermodynamically consistent, mass-and-charge balanced, kinetic model of mitochondrial ROS homeostasis focused on redox sites of electron transport chain complexes I, II, and III. The model was calibrated and corroborated using comprehensive data sets relevant to ROS homeostasis. The model predicts that complex I ROS production dominates other sources under conditions favoring a high membrane potential with elevated NADH and QH2 levels. In general, complex I contributes to significant levels of ROS production under pathological conditions, while complexes II and III are responsible for basal levels of ROS production, especially when QH2 levels are elevated. The model also reveals that hydrogen peroxide production by complex I underlies the non-linear relationship between ROS emission and O2 at low O2 concentrations. Lastly, the model highlights the need to quantify scavenging system activity under different conditions to establish a complete picture of mitochondrial ROS homeostasis. In summary, we describe the individual contributions of the ETS complex redox sites to total ROS emission in mitochondria respiring under various combinations of NADH- and Q-linked respiratory fuels under varying workloads.

scholarly journals Omega‐3‐producing fat‐1 transgenic mice display reduced complex I‐associated hydrogen peroxide production and enzyme activity

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Jon Ramsey ◽  
Kristina Weber ◽  
Darren Hwee ◽  
Alison Van Eenennaam ◽  
J. Bruce German ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Enzyme Activity ◽  
Transgenic Mice ◽  
Complex I ◽  
Omega 3 ◽  
Hydrogen Peroxide Production

Nitric oxide, cytochrome c and mitochondria

1999 ◽  
Vol 66 ◽  
pp. 17-25 ◽  
Author(s):  
Guy C. Brown ◽  
Vilmante Borutaite
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Cytochrome C ◽  
Cytochrome Oxidase ◽  
Protease Activity ◽  
Complex I ◽  
Glutamate Release ◽  
Nerve Terminals ◽  
No Inhibition ◽  
Brain Nerve Terminals

Nitric oxide (NO) and its derivative, peroxynitrite (ONOO-), inhibit mitochondrial respiration, and this inhibition may contribute to both the physiological and cytotoxic actions of NO. Nanomolar concentrations of NO rapidly and reversibly inhibited cytochrome oxidase in competition with oxygen, as shown with isolated cytochrome oxidase, mitochondria, brain nerve terminals and cells. Cultured astrocytes and macrophages activated (by cytokines and endotoxin) to express the inducible form of NO synthase produced up to 1 μM NO, and inhibited their own respiration and that of co-incubated cells via reversible NO inhibition of cytochrome oxidase. NO-induced inhibition of respiration in brain nerve terminals resulted in rapid glutamate release, which might contribute to the neurotoxicity of NO. NO inhibition of cytochrome oxidase is reversible; however, incubation of cells with NO donors for 4 hours resulted in an inhibition of complex I, which was reversible by light and thiol reagents and may be due to nitrosylation of thiols in complex I. NO also caused the acute inhibition of catalase, stimulation of hydrogen peroxide production by mitochondria, and reaction with hydrogen peroxide on superoxide dismutase to produce peroxynitrite. Peroxynitrite inhibited complexes I, II and V (the ATP synthase), aconitase, creatine kinase, and increases the proton leak in isolated mitochondria. Peroxynitrite also caused opening of the permeability transition pore, resulting in the release of cytochrome c, which might then trigger apoptosis. Hypoxia/ischaemia also resulted in an acute reversible inhibition of cytochrome oxidase. Heart ischaemia caused the release of cytochrome c from mitochondria into the cytosol, and at the same time caspase-3-like-protease activity was activated in the cytoplasm. Addition of cytochrome c to non-ischaemic cytosol also caused activation of this protease activity, suggesting that caspase activation and consequent apoptosis is at least partly a result of this cytochrome c release.

Sign in / Sign up

Export Citation Format

Share Document