ArticleFree radical biology & medicine2013
Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Mitochondrial Reactive Oxygen Species (mROS) Generation and Cancer:International journal of nanomedicine · 2025Review
- Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT-1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production.Journal of neurochemistry · 2025Article
- Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PMEnvironmental pollution (Barking, Essex : 1987) · 2024Article
- Reactive Oxygen Species Generation by Reverse Electron Transfer at Mitochondrial Complex I Under Simulated Early Reperfusion Conditions.bioRxiv : the preprint server for biology · 2023Article
- Site IQ in mitochondrial complex I generates S1QEL-sensitive superoxide/hydrogen peroxide in both the reverse and forward reactions.The Biochemical journal · 2023Article
- Reactive oxygen species formation and its effect on CD4Frontiers in immunology · 2023Review
- Naked Mole-Rat Cortex Maintains Reactive Oxygen Species Homeostasis DuringCurrent neuropharmacology · 2023Article
- Artificial neural network applied to fragile X-associated tremor/ataxia syndrome stage diagnosis based on peripheral mitochondrial bioenergetics and brain imaging outcomes.Scientific reports · 2022Article
- Effects of sugars, fatty acids and amino acids on cytosolic and mitochondrial hydrogen peroxide release from liver cells.Free radical biology & medicine · 2022Article
- The metabolic fate of oxaliplatin in the biological milieu investigated duringFrontiers in cell and developmental biology · 2022Article
- Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3.Iranian journal of basic medical sciences · 2022Article
- The Roles of Coenzyme Q in Disease: Direct and Indirect Involvement in Cellular Functions.International journal of molecular sciences · 2021Review
- Review
- Functions of ROS in Macrophages and Antimicrobial Immunity.Antioxidants (Basel, Switzerland) · 2021Review
- Protective Effect of Mitochondria-Targeted Antioxidants against Inflammatory Response to Lipopolysaccharide Challenge: A Review.Pharmaceutics · 2021Review
- Production of superoxide and hydrogen peroxide in the mitochondrial matrix is dominated by site IRedox biology · 2020Article
- IACS-010759, a potent inhibitor of glycolysis-deficient hypoxic tumor cells, inhibits mitochondrial respiratory complex I through a unique mechanism.The Journal of biological chemistry · 2020Article
- BAD sensitizes breast cancer cells to docetaxel with increased mitotic arrest and necroptosis.Scientific reports · 2020Article
- The use of site-specific suppressors to measure the relative contributions of different mitochondrial sites to skeletal muscle superoxide and hydrogen peroxide production.Redox biology · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial production of reactive oxygen species is often considered an unavoidable consequence of aerobic metabolism and currently cannot be manipulated without perturbing oxidative phosphorylation. Antioxidants are widely used to suppress effects of reactive oxygen species after formation, but they can never fully prevent immediate effects at the sites of production. To identify site-selective inhibitors of mitochondrial superoxide/H2O2 production that do not interfere with mitochondrial energy metabolism, we developed a robust small-molecule screen and secondary profiling strategy. We describe the discovery and characterization of a compound (N-cyclohexyl-4-(4-nitrophenoxy)benzenesulfonamide; CN-POBS) that selectively inhibits superoxide/H2O2 production from the ubiquinone-binding site of complex I (site I(Q)) with no effects on superoxide/H2O2 production from other sites or on oxidative phosphorylation. Structure/activity studies identified a core structure that is important for potency and selectivity for site I(Q). By employing CN-POBS in mitochondria respiring on NADH-generating substrates, we show that site I(Q) does not produce significant amounts of superoxide/H2O2 during forward electron transport on glutamate plus malate. Our screening platform promises to facilitate further discovery of direct modulators of mitochondrially derived oxidative damage and advance our ability to understand and manipulate mitochondrial reactive oxygen species production under both normal and pathological conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.