Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I

2009 ◽  
Vol 41 (8-9) ◽  
pp. 1697-1707 ◽  
Author(s):  
Lydie Plecitá-Hlavatá ◽  
Jan Ježek ◽  
Petr Ježek
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Proton Pumping ◽  
Mitochondrial Matrix ◽  
Anti Oxidant

scholarly journals Functional basis of electron transport within photosynthetic complex I

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katherine H. Richardson ◽  
John J. Wright ◽  
Mantas Šimėnas ◽  
Jacqueline Thiemann ◽  
Ana M. Esteves ◽  
...  
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Proton Pumping ◽  
Reduction Potentials ◽  
Large Size ◽  
Complex Functions ◽  
High Lability ◽  
Respiratory Complex I ◽  
Double Electron Electron Resonance ◽  
Insight Into

AbstractPhotosynthesis and respiration rely upon a proton gradient to produce ATP. In photosynthesis, the Respiratory Complex I homologue, Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes. However, little is known about the PS-CI molecular mechanism and attempts to understand its function have previously been frustrated by its large size and high lability. Here, we overcome these challenges by pushing the limits in sample size and spectroscopic sensitivity, to determine arguably the most important property of any electron transport enzyme – the reduction potentials of its cofactors, in this case the iron-sulphur clusters of PS-CI (N0, N1 and N2), and unambiguously assign them to the structure using double electron-electron resonance. We have thus determined the bioenergetics of the electron transfer relay and provide insight into the mechanism of PS-CI, laying the foundations for understanding of how this important bioenergetic complex functions.

scholarly journals Functional basis of electron transport within photosynthetic complex I

2021 ◽  
Author(s):  
Katherine H. Richardson ◽  
John J. Wright ◽  
Mantas Šimėnas ◽  
Jacqueline Thiemann ◽  
Ana M. Esteves ◽  
...  
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Cell Types ◽  
Proton Pumping ◽  
Higher Plant ◽  
Reduction Potentials ◽  
Large Size ◽  
Complex Functions ◽  
High Lability ◽  
Double Electron Electron Resonance

AbstractPhotosynthesis and respiration rely upon a proton gradient to produce ATP. In photosynthesis, the Respiratory Complex I homologue, Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes, and is fundamental to bioenergetics in photosynthetic bacteria and some higher plant cell types. However, little is known about the PS-CI molecular mechanism and attempts to understand its function have previously been frustrated by its large size and high lability. Here, we overcome these challenges by pushing the limits in sample size and spectroscopic sensitivity, to determine arguably the most important property of any electron transport enzyme – the reduction potentials of its cofactors, in this case the iron-sulphur clusters of PS-CI, and unambiguously assign them to the structure using double electron-electron resonance (DEER). We have thus determined the bioenergetics of the electron transfer relay and provide insight into the mechanism of PS-CI, laying the foundations for understanding of how this important bioenergetic complex functions.

scholarly journals Paracoccus denitrificans: a genetically tractable model system for studying respiratory complex I

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Owen D. Jarman ◽  
Olivier Biner ◽  
John J. Wright ◽  
Judy Hirst
Keyword(s):  
Complex I ◽  
Paracoccus Denitrificans ◽  
Model System ◽  
Proton Pumping ◽  
Model Systems ◽  
Metabolic Enzyme ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inner Mitochondrial Membrane

AbstractMitochondrial complex I (NADH:ubiquinone oxidoreductase) is a crucial metabolic enzyme that couples the free energy released from NADH oxidation and ubiquinone reduction to the translocation of four protons across the inner mitochondrial membrane, creating the proton motive force for ATP synthesis. The mechanism by which the energy is captured, and the mechanism and pathways of proton pumping, remain elusive despite recent advances in structural knowledge. Progress has been limited by a lack of model systems able to combine functional and structural analyses with targeted mutagenic interrogation throughout the entire complex. Here, we develop and present the α-proteobacterium Paracoccus denitrificans as a suitable bacterial model system for mitochondrial complex I. First, we develop a robust purification protocol to isolate highly active complex I by introducing a His6-tag on the Nqo5 subunit. Then, we optimize the reconstitution of the enzyme into liposomes, demonstrating its proton pumping activity. Finally, we develop a strain of P. denitrificans that is amenable to complex I mutagenesis and create a catalytically inactive variant of the enzyme. Our model provides new opportunities to disentangle the mechanism of complex I by combining mutagenesis in every subunit with established interrogative biophysical measurements on both the soluble and membrane bound enzymes.

scholarly journals Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency

2017 ◽  
Vol 216 (3) ◽  
pp. 695-708 ◽  
Author(s):  
Melissa Vos ◽  
Ann Geens ◽  
Claudia Böhm ◽  
Liesbeth Deaulmerie ◽  
Jef Swerts ◽  
...  
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Fatty Acid Synthase ◽  
Induced Pluripotent Stem Cell ◽  
Mitochondrial Inner Membrane ◽  
Mitochondrial Defects ◽  
Mouse Cells ◽  
Induced Pluripotent ◽  
Specific Lipid ◽  
Pharmacologic Inhibition

PINK1 is mutated in Parkinson’s disease (PD), and mutations cause mitochondrial defects that include inefficient electron transport between complex I and ubiquinone. Neurodegeneration is also connected to changes in lipid homeostasis, but how these are related to PINK1-induced mitochondrial dysfunction is unknown. Based on an unbiased genetic screen, we found that partial genetic and pharmacological inhibition of fatty acid synthase (FASN) suppresses toxicity induced by PINK1 deficiency in flies, mouse cells, patient-derived fibroblasts, and induced pluripotent stem cell–derived dopaminergic neurons. Lower FASN activity in PINK1 mutants decreases palmitate levels and increases the levels of cardiolipin (CL), a mitochondrial inner membrane–specific lipid. Direct supplementation of CL to isolated mitochondria not only rescues the PINK1-induced complex I defects but also rescues the inefficient electron transfer between complex I and ubiquinone in specific mutants. Our data indicate that genetic or pharmacologic inhibition of FASN to increase CL levels bypasses the enzymatic defects at complex I in a PD model.

Electron transport pathways for the oxidation of endogenous substrate(s) in Acidithiobacillus ferrooxidans

2006 ◽  
Vol 52 (4) ◽  
pp. 317-327 ◽  
Author(s):  
Yongqiang Chen ◽  
Isamu Suzuki
Keyword(s):  
Electron Transport ◽  
Electron Acceptor ◽  
Acidithiobacillus Ferrooxidans ◽  
Complex I ◽  
Iron Chelators ◽  
Endogenous Respiration ◽  
Sugar Alcohols ◽  
Transport Pathways ◽  
Endogenous Substrate ◽  
Transport Inhibitors

Oxidation of endogenous substrate(s) of Acidithiobacillus ferrooxidans with O2 or Fe3+ as electron acceptor was studied in the presence of uncouplers and electron transport inhibitors. Endogenous substrate was oxidized with a respiratory quotient (CO2 produced/O2 consumed) of 1.0, indicating its carbohydrate nature. The oxidation was inhibited by complex I inhibitors (rotenone, amytal, and piericidin A) only partially, but piericidin A inhibited the oxidation with Fe3+ nearly completely. The oxidation was stimulated by uncouplers, and the stimulated activity was more sensitive to inhibition by complex I inhibitors. HQNO (2-heptyl-4-hydroxyquinoline N-oxide) also stimulated the oxidation, and the stimulated respiration was more sensitive to KCN inhibition than uncoupler stimulated respiration. Fructose, among 20 sugars and sugar alcohols including glucose and mannose, was oxidized with a CO2/O2 ratio of 1.0 by the organism. Iron chelators in general stimulated endogenous respiration, but some of them reduced Fe3+ chemically, introducing complications. The results are discussed in view of a branched electron transport system of the organism and its possible control.Key words: Acidithiobacillus ferrooxidans, endogenous respiration, uncouplers, electron transport.

New inhibitors of Complex I of the mitochondrial electron transport chain with activity as pesticides

1994 ◽  
Vol 22 (1) ◽  
pp. 230-233 ◽  
Author(s):  
Robert M. Hollingworth ◽  
Kabeer I. Ahammadsahib ◽  
G. Gadelhak ◽  
J. L. McLaughlin
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Electron Transport Chain ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain

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 Large-scale chromatographic purification of F1F0-ATPase and complex I from bovine heart mitochondria

1996 ◽  
Vol 318 (1) ◽  
pp. 343-349 ◽  
Author(s):  
Susan K BUCHANAN ◽  
John E. WALKER
Keyword(s):  
Complex I ◽  
Large Scale ◽  
Gel Filtration ◽  
Atp Synthesis ◽  
Lipid Vesicles ◽  
Proton Pumping ◽  
Heart Mitochondria ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Bovine Heart ◽  
F1fo Atpase

A new chromatographic procedure has been developed for the isolation of F1Fo-ATPase and NADH:ubiquinone oxidoreductase (complex I) from a single batch of bovine heart mitochondria. The method employed dodecyl β-Δ-maltoside, a monodisperse, homogeneous detergent in which many respiratory complexes exhibit high activity, for solubilization and subsequent purification by ammonium sulphate fractionation and column chromatography. A combination of anion-exchange, gel-filtration, and dye-ligand affinity chromatography was used to purify both complexes to homogeneity. The F1Fo-ATPase preparation contains only the 16 known subunits of the enzyme. It has oligomycin-sensitive ATP hydrolysis activity and, as demonstrated elsewhere, when reconstituted into lipid vesicles it is capable of ATP-dependent proton pumping and of ATP synthesis driven by a proton gradient [Groth and Walker (1996) Biochem. J. 318, 351–357]. The complex I preparation contains all of the subunits identified in other preparations of the enzyme, and has rotenone-sensitive NADH:ubiquinone oxidoreductase and NADH:ferricyanide oxidoreductase activities. The procedure is rapid and reproducible, yielding 50–80 mg of purified F1Fo-ATPase and 20–40 mg of purified complex I from 1 g of mitochondrial membranes. Both preparations are devoid of phospholipids, and gel filtration and dynamic light scattering experiments indicate that they are monodisperse. Therefore, the preparations fulfil important prerequisites for structural analysis.

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