Quinone Reduction Research Articles

Quantum Chemical and QM/MM Models in Biochemistry.

Quantum chemical (QC) calculations provide a basis for deriving a microscopic understanding of enzymes and photobiological systems. Here we describe how QC models can be used to explore the electronic structure, dynamics, and energetics of biomolecules. We introduce the hybrid quantum mechanics/classical mechanics (QM/MM) approach, where a quantum mechanically described system of interest is embedded in a classically described force field representation of the biochemical surroundings. We also discuss the QM cluster model approach, as well as embedding theories, that provide complementary methodologies to model quantum mechanical effects in biomolecules. The chapter also provides some practical guides for building quantum biochemical models using the quinone reduction catalysis in respiratory complex I and a model reaction in solution as examples.

The cytochrome b lysine 329 residue is critical for ubihydroquinone oxidation and proton release at the Qo site of bacterial cytochrome bc1

The ubihydroquinone:cytochrome (cyt) c oxidoreductase (or cyt bc1) is an important enzyme for photosynthesis and respiration. In bacteria like Rhodobacter capsulatus, this membrane complex has three subunits, the iron‑sulfur protein (ISP) with its Fe2S2 cluster, cyt c1 and cyt b, forming two catalytic domains, the Qo (hydroquinone (QH2) oxidation) and Qi (quinone (Q) reduction) sites. At the Qo site, the electron transfer pathways originating from QH2 oxidation are known, but their associated proton release routes are less well defined. Earlier, we demonstrated that the His291 of cyt b is important for this latter process. In this work, using the bacterial cyt bc1 and site directed mutagenesis, we show that Lys329 of cyt b is also critical for electron and proton transfer at the Qo site. Of the mutants examined, Lys329Arg was photosynthesis proficient and had quasi-wild type cyt bc1 activity. In contrast, the Lys329Ala and Lys329Asp were photosynthesis-impaired and contained defective but assembled cyt bc1. In particular, the bifurcated electron transfer and associated proton(s) release reactions occurring during QH2 oxidation were drastically impaired in Lys329Asp mutant. Furthermore, in silico docking studies showed that in this mutant the location and the H-bonding network around the Fe2S2 cluster of ISP on cyt b surface was different than the wild type enzyme. Based on these experimental findings and theoretical considerations, we propose that the presence of a positive charge at position 329 of cyt b is critical for efficient electron transfer and proton release for QH2 oxidation at the Qo site of cyt bc1.

An electrogenic redox loop in sulfate reduction reveals a likely widespread mechanism of energy conservation

The bioenergetics of anaerobic metabolism frequently relies on redox loops performed by membrane complexes with substrate- and quinone-binding sites on opposite sides of the membrane. However, in sulfate respiration (a key process in the biogeochemical sulfur cycle), the substrate- and quinone-binding sites of the QrcABCD complex are periplasmic, and their role in energy conservation has not been elucidated. Here we show that the QrcABCD complex of Desulfovibrio vulgaris is electrogenic, as protons and electrons required for quinone reduction are extracted from opposite sides of the membrane, with a H+/e− ratio of 1. Although the complex does not act as a H+-pump, QrcD may include a conserved proton channel leading from the N-side to the P-side menaquinone pocket. Our work provides evidence of how energy is conserved during dissimilatory sulfate reduction, and suggests mechanisms behind the functions of related bacterial respiratory complexes in other bioenergetic contexts.

Efficient Photochemical Reduction of Quinone into Hydroquinone Promoted by Imidazolyl N-H Proton

Photochemical reductions of imidazole-conjugated quinones in acetonitrile solutions containing [Ru(bpy)3]2+ (bpy: 2.2′-bipyridine) as a photosensitizer and triethanolamine as an electron donor sele...

Self-Adaptable Quinone-Quinol Exchange Mechanism of Photosystem II.

The step of plastoquinone (PQ) reduction to plastoquinol (PQH2) can regulate the photoreaction rate of photosystem II (PSII). To experimentally unravel the PQ-PQH2 exchange mechanism of PSII, we investigate the reaction kinetics of plant PSII membranes and the subunits-trimmed PSII core complexes with various PQ analogues and directly probe the reductions of PQ and other quinones by 257 nm resonance Raman scattering. Two phases of quinone concentration effect on the reaction rate originate from the quinone-quinol exchange mechanism. The results indicate that high concentrations of quinone, more than one movable quinone molecule per PSII reaction center, could trigger quinone-quinol exchange adapting to the unidirectional route: quinones enter through channel I and/or III, and quinols leave through channel II. A weak quinone binding site near QB probably plays a crucial role in pushing quinone-quinol exchange forward in the unidirectional route. Our work provides experimental proofs demonstrating a self-adaptable quinone-quinol exchange mechanism of PSII.

Voltammetric Determination of Amino Acids Based on the Measurement of Reduction Prepeak of Quinone Caused by Surplus Acid after Neutralization

AbstractIn the voltammetric reduction of quinone, such as 3,5‐di‐tert‐butyl‐1,2‐benzoquinone (DBBQ), in the presence of HCl, a reduction prepeak of DBBQ caused by HCl can be observed on a voltammogram. Here, we have shown that the prepeak height of DBBQ is linearly decreased with increasing concentrations of amino acid in an electrolyte solution when this voltammetry is performed after neutralization between amino acids and excess HCl. This finding is based on a concept of acid‐base back titration of amino acids with excess HCl where surplus HCl gives a reduction prepeak of DBBQ. In this study, the reduction behaviors of DBBQ in the presence of amino acids and HCl have been provided to develop a novel electroanalytical method for the determining of amino acids. Electrochemical detection of 20 kinds of α‐amino acids, including less electroactive ones, has been achieved using a bare plastic formed carbon working electrode. Moreover, a flow injection analysis with electrochemical detection system using a glassy carbon working electrode is developed based on the present detection principle, and it has been applied to the determination of glutamine in an L‐glutamine granulated powder.

Impact of 17β-estradiol on complex I kinetics and H2O2 production in liver and skeletal muscle mitochondria

Naturally or surgically induced postmenopausal women are widely prescribed estrogen therapies to alleviate symptoms associated with estrogen loss and to lower the subsequent risk of developing metabolic diseases, including diabetes and nonalcoholic fatty liver disease. However, the molecular mechanisms by which estrogens modulate metabolism across tissues remain ill-defined. We have previously reported that 17β-estradiol (E2) exerts antidiabetogenic effects in ovariectomized (OVX) mice by protecting mitochondrial and cellular redox function in skeletal muscle. The liver is another key tissue for glucose homeostasis and a target of E2 therapy. Thus, in the present study we determined the effects of acute loss of ovarian E2 and E2 administration on liver mitochondria. In contrast to skeletal muscle mitochondria, E2 depletion via OVX did not alter liver mitochondrial respiratory function or complex I (CI) specific activities (NADH oxidation, quinone reduction, and H2O2 production). Surprisingly, in vivo E2 replacement therapy and in vitro E2 exposure induced tissue-specific effects on both CI activity and on the rate and topology of CI H2O2 production. Overall, E2 therapy protected and restored the OVX-induced reduction in CI activity in skeletal muscle, whereas in liver mitochondria E2 increased CI H2O2 production and decreased ADP-stimulated respiratory capacity. These results offer novel insights into the tissue-specific effects of E2 on mitochondrial function.

Targeted Structure-Activity Analysis of Endochin-like Quinolones Reveals Potent Qi and Qo Site Inhibitors of Toxoplasma gondii and Plasmodium falciparum Cytochrome bc1 and Identifies ELQ-400 as a Remarkably Effective Compound against Acute Experimental Toxoplasmosis.

Cytochrome bc1 inhibitors have been broadly studied as human and veterinary medicines and agricultural fungicides. For the most part, cytochrome bc1 inhibitors compete with ubiquinol at the ubiquinol oxidation (Qo) site or with ubiquinone at the quinone reduction (Qi) site. 4(1 H)-Quinolones with 3-position substituents may inhibit either site based on quinolone ring substituents. 4(1 H)-Quinolones that inhibit the Qi site are highly effective against toxoplasmosis, malaria, and babesiosis and do not inhibit human cytochrome bc1. We tested a series of 4(1 H)-Quinolones against wild-type and drug resistant strains of Toxoplasma gondii and Plasmodium falciparum. These experiments identified very potent compounds that inhibit T. gondii proliferation at picomolar concentrations. The most potent compounds target the Qo site, and for these compounds, an alkyl side chain confers potency against T. gondii greater than that of bulkier side chains. Our experiments also show that substituents on the quinolone ring influenced selectivity between T. gondii and P. falciparum and between Qo and Qi site-mediated activity. Comparison of the parasite cytochrome b sequences identified amino acids that are associated with drug resistance in P. falciparum that exist naturally in wild-type T. gondii. These underlying differences may influence drug susceptibility. Finally, a Qo site active 4(1 H)-quinolone-3-diarylether tested in a murine model of toxoplasmosis was superior to atovaquone, resulting in survival from Type I strain T. gondii infection. These experiments identify highly effective compounds for toxoplasmosis and provide valuable insight into the structure-activity relationship of cytochrome bc1 inhibitors.

Redox-coupled quinone dynamics in the respiratory complex I

Complex I couples the free energy released from quinone (Q) reduction to pump protons across the biological membrane in the respiratory chains of mitochondria and many bacteria. The Q reduction site is separated by a large distance from the proton-pumping membrane domain. To address the molecular mechanism of this long-range proton-electron coupling, we perform here full atomistic molecular dynamics simulations, free energy calculations, and continuum electrostatics calculations on complex I from Thermus thermophilus We show that the dynamics of Q is redox-state-dependent, and that quinol, QH2, moves out of its reduction site and into a site in the Q tunnel that is occupied by a Q analog in a crystal structure of Yarrowia lipolytica We also identify a second Q-binding site near the opening of the Q tunnel in the membrane domain, where the Q headgroup forms strong interactions with a cluster of aromatic and charged residues, while the Q tail resides in the lipid membrane. We estimate the effective diffusion coefficient of Q in the tunnel, and in turn the characteristic time for Q to reach the active site and for QH2 to escape to the membrane. Our simulations show that Q moves along the Q tunnel in a redox-state-dependent manner, with distinct binding sites formed by conserved residue clusters. The motion of Q to these binding sites is proposed to be coupled to the proton-pumping machinery in complex I.

Nitric oxide alleviates toxicity of hexavalent chromium on tall fescue and improves performance of photosystem II

Tall fescue (Festuca arundinacea Schreb) was widely studied for phytoremediation of organic or heavy metal contaminated soils. However, there is still little information concerning toxicity of chromium (Cr) to tall fescue and roles of nitric oxide (NO) in plants against Cr(VI) stress. In this study, different Cr(VI) treatments (0, 1, 5 and 10 mg/L Cr(VI)) and NO treatments were applied with different combinations in hydroponics culture and their interactions to tall fescue were studied. Specifically, 100 µM sodium nitroprusside (SNP) and 100 µM NG-nitro-L-arginine-methyl ester (L-NAME) treatments were used to apply exogenous NO or inhibit synthesis of NO respectively. Our results showed that tall fescue exhibits comparable Cr(VI) tolerance as wheat (Triticum aestivum L.). Additionally, Cr(VI) accumulation in tall fescue leaves were carefully studied and discussed. Moreover, we observed the significantly increased reactive oxygen species (ROS) contents of tall fescue when subjected to Cr(VI) stress, as well as decreased photosynthetic activities induced by Cr(VI) stress by methods of chlorophyll a fluorescence transient, slow chlorophyll fluorescence kinetics and rapid light response curves. Decreased behaviors of photosynthetic activities may due to destruction of antennae pigments by Cr(VI), ROS burst induced by Cr(VI), and down regulation of photosystem II (PSII) by non-photochemical quenching to avoid over reduction of quinone A, which could be considered as an important strategy to cope with Cr(VI) stress. Meanwhile, exogenous NO treatment improves overall physiological and photosynthetic behaviors of tall fescue against Cr(VI) stress. Moreover, increased translocation factors and improved Cr(VI) tolerance of plants under exogenous NO treatment suggest that SNP treatment could be a useful application for Cr phytoremediation.

Mechanisms of photochemical reactions of para-benzoquinones with thiols

The mechanisms of quinone reduction by thiols containing α-hydrogen atoms were established using chemically induced dynamic nuclear polarization effects. It was found that substituents in the quinone nucleus change the nature of the primary radical pair. In the photolysis of 2,6-dimethyl-1,4-benzoquinone (1), the radical pair consists of semiquinone and thioalkyl radicals, whereas in the case of 2,6-diphenyl-1,4-benzoquinone (2), the radical pair is composed of semiquinone and thiyl radicals. Quinone 2 is readily photolyzed with any thiol to give dibenzofuran derivative as the final products.

(Invited) Hydrogen Bonding Effects at the Organic-Water Interface of Aqueous Toluene Droplets Investigated By Particle Collision Electrochemistry

This work reports on the hydrogen bonding effects induced by water solvation in aqueous toluene droplets studied by Particle Collision Electrochemistry (PCE). The latter approach is an emerging methodology employed to characterize microscopic particles that collide with the surface of an ultramicroelectrode as a result of Brownian motion. The ability of PCE to yield in-situ kinetic and thermodynamic information from single collision events has led to fundamental studies of nanoparticle electrochemistry which now is recognized as a sub-field in electrochemistry dubbed as single entity electrochemistry, due to the wide range of probes that can be investigated. Herein, the reversal of hydrogen bonding affinity between quinone phenolate di-anions (Q2-) and carboxylic acids, induced by water in micrometer-size droplets of toluene is reported. Such an effect is revealed by the two-electron reduction of the hydrophobic quinone (Q) tetrachoro-1,4-benzoquinone to Q2- inside the toluene droplets, when performed in the presence of carboxylic acids that partition differently between the aqueous and organic phases. In bulk toluene, the hydrogen bonding affinity of Q2- for acetic acid (pKa = 4.8) is higher than for oleic acid (pKa = 9.9). However, such trend is reversed in emulsified toluene droplets due to preferential solvation of acetic acid by the surrounding water. The goal of this work is two-fold: first, to illustrate a subtle yet consequential water effect that arises from heterogeneous micro-confinement of organic-water phases, and second, to demonstrate how mechanistic information in such interfaces can be extracted from PCE.

Mechanism of Two-/Four-Electron Reduction of Nitroaromatics by Oxygen-Insensitive Nitroreductases: The Role of a Non-Enzymatic Reduction Step.

Oxygen-insensitive NAD(P)H:nitroreductases (NR) reduce nitroaromatics (Ar-NO2) into hydroxylamines (Ar-NHOH) through nitroso (Ar-NO) intermediates. Ar-NO may be reduced both enzymatically and directly by reduced nicotinamide adenine dinucleotide or its phosphate NAD(P)H, however, it is unclear which process is predominant in catalysis of NRs. We found that E. coli NR-A (NfsA) oxidizes 2 mol of NADPH per mol of 2,4,6-trinitrotoluene (TNT) and 4 mol of NADPH per mol of tetryl. Addition of ascorbate, which reduces Ar-NO into Ar-NHOH, changes the stoichiometry NADPH/Ar-NO2 into 1:1 (TNT) and 2:1 (tetryl), and decreases the rate of NADPH oxidation. Ascorbate does not interfere with the oxidation of NADPH during reduction of quinones by NfsA. Our analysis of ascorbate inhibition patterns and both enzymatic and non-enzymatic reduction of nitrosobenzene suggests that direct reduction of Ar-NO by NADPH rather than enzymatic reduction is the predominant mechanism during nitroaromatic reduction.

How inter-subunit contacts in the membrane domain of complex I affect proton transfer energetics

The respiratory complex I is a redox-driven proton pump that employs the free energy released from quinone reduction to pump protons across its complete ca. 200 Å wide membrane domain. Despite recently resolved structures and molecular simulations, the exact mechanism for the proton transport process remains unclear. Here we combine large-scale molecular simulations with quantum chemical density functional theory (DFT) models to study how contacts between neighboring antiporter-like subunits in the membrane domain of complex I affect the proton transfer energetics. Our combined results suggest that opening of conserved Lys/Glu ion pairs within each antiporter-like subunit modulates the barrier for the lateral proton transfer reactions. Our work provides a mechanistic suggestion for key coupling effects in the long-range force propagation process of complex I.

Quinones and nitroaromatic compounds as subversive substrates of Staphylococcus aureus flavohemoglobin

In microorganisms, flavohemoglobins (FHbs) containing FAD and heme (Fe3+, metHb) convert NO. into nitrate at the expense of NADH and O2. FHbs contribute to bacterial resistance to nitrosative stress. Therefore, inhibition of FHbs functions may decrease the pathogen virulence. We report here a kinetic study of the reduction of quinones and nitroaromatic compounds by S. aureus FHb. We show that this enzyme rapidly reduces quinones and nitroaromatic compounds in a mixed single- and two-electron pathway. The reactivity of nitroaromatics increased upon an increase in their single-electron reduction potential (E17), whereas the reactivity of quinones poorly depended on their E17 with a strong preference for a 2-hydroxy-1,4-naphthoquinone structure. The reaction followed a ‘ping-pong’ mechanism. In general, the maximal reaction rates were found lower than the maximal presteady-state rate of FAD reduction by NADH and/or of oxyhemoglobin (HbFe2+O2) formation (~130 s−1, pH 7.0, 25 °C), indicating that the enzyme turnover is limited by the oxidative half-reaction. The turnover studies showed that quinones prefreqently accept electrons from reduced FAD, and not from HbFe2+O2. These results suggest that quinones and nitroaromatics act as ‘subversive substrates’ for FHb, and may enhance the cytotoxicity of NO. by formation of superoxide and by diverting the electron flux coming from reduced FAD. Because quinone reduction rate was increased by FHb inhibitors such as econazole, ketoconazole, and miconazole, their combined use may represent a novel chemotherapeutical approach.

Magnetic multiwalled carbon nanotubes as nanocarrier tags for sensitive determination of fetuin in saliva

This paper reports the development and performance of an electrochemical immunosensor using magnetic multiwalled carbon nanotubes (m-MWCNTs) as nanocarrier tags for the determination of human fetuin A (HFA), a relevant biomarker of obesity, insulin resistance, and type-2 diabetes as well as for pancreatic and liver cancers and inflammatory processes. Screen-printed carbon electrodes were grafted with p-aminobezoic acid and streptavidin was covalently immobilized on the electrode surface. A biotinylated capture antibody was immobilized through streptavidin-biotin interaction and a sandwich assay configuration was implemented using m-MWCNTs conjugated with HRP and anti-HFA antibodies as the detection label. The determination of HFA was accomplished by measuring the current produced by the electrochemical reduction of benzoquinone at −200 mV upon addition of H2O2 as HRP substrate. The prepared m-MWCNTs were characterized by SEM, TEM, XRD and EDS. All the steps involved in the immunosensor preparation were monitored by electrochemical impedance spectroscopy and cyclic voltammetry. A linear calibration plot for HFA was found between 20 and 2000 pg/mL with a LOD value of 16 pg/mL. This performance is notably better than that reported for an ELISA kit and a chronoimpedimetric immunosensor. The favorable contribution of m-MWCNTs in comparison with MWCNTs without incorporated magnetic particles to this excellent analytical performance is also highlighted. The immunosensor selectivity against other proteins and potentially interfering compounds was excellent. In addition, the usefulness of the immunosensor was demonstrated by the analysis of HFA in saliva with minimal sample treatment.

A novel enzyme of type VI sulfide:quinone oxidoreductases in purple sulfur photosynthetic bacteria.

Sulfide detoxification can be catalyzed by ancient membrane-bound flavoproteins, sulfide:quinone oxidoreductases (Sqr), which have important roles in sulfide homeostasis and sulfide-dependent energy conservation processes by transferring electrons from sulfide to respiratory or photosynthetic membrane electron flow. Sqr enzymes have been categorized into six groups. Several members of the groups I, II, III, and V are well-known, but type IV and VI Sqrs are, as yet, uncharacterized or hardly characterized at all. Here, we report detailed characterization of a type VI sulfide:quinone oxidoreductase (TrSqrF) from a purple sulfur bacterium, Thiocapsa roseopersicina. Phylogenetic analysis classified this enzyme in a special group composed of SqrFs of endosymbionts, while a weaker relationship could be observed with SqrF of Chlorobaculum tepidum which is the only type VI enzyme characterized so far. Directed mutagenesis experiments showed that TrSqrF contributed substantially to the sulfide:quinone oxidoreductase activity of the membranes. Expression of the sqrF gene could be induced by sulfide. Homologous recombinant TrSqrF protein was expressed and purified from the membranes of a SqrF-deleted T. roseopersicina strain. The purified protein contains redox-active covalently bound FAD cofactor. The recombinant TrSqrF enzyme catalyzes sulfur-dependent quinone reduction and prefers ubiquinone-type quinone compounds. Kinetic parameters of TrSqrF show that the affinity of the enzyme is similar to duroquinone and decylubiquinone, but the reaction has substantially lower activation energy with decylubiquinone, indicating that the quinone structure has an effect on the catalytic process. TrSqrF enzyme affinity for sulfide is low, therefore, in agreement with the gene expressional analyis, SqrF could play a role in energy-conserving sulfide oxidation at high sulfide concentrations. TrSqrF is a good model enzyme for the subgroup of type VI Sqrs of endosymbionts and its characterization might provide deeper insight into the molecular details of the ancient, anoxic, energy-gaining processes using sulfide as an electron donor.

(Invited) Controlling the ORR with Proton Kinetics and Non-Precious Metal Catalysts

This talk addresses the Oxygen Reduction Reaction (ORR) a reaction important in fuel cells. We use a kinetic isotope effect analysis to more fully elucidate both the ORR and OER mechanisms for both precious metal and non-precious metal systems. We develop a new platform based on a hybrid bilayer membrane (HBM) to more generally address proton-coupled electron transfer (PCET) reactions, of which the ORR is one, and show that ORR speciation can be controlled by tuning the kinetics of proton transfer. The HBM is shown to illuminate other electrochemical processes, such as anion transport, and quinone reduction speciation. We develop new non-precious metal catalysts for the ORR based on carbon encapsulated superparamagetic Fe nanoparticles. We use surface chemistry to develop new insight into the origin of activity on these constructs.

The Proline Cycle As a Potential Cancer Therapy Target.

Interest in how proline contributes to cancer biology is expanding because of the emerging role of a novel proline metabolic cycle in cancer cell survival, proliferation, and metastasis. Proline biosynthesis and degradation involve the shared intermediate Δ1-pyrroline-5-carboxylate (P5C), which forms l-glutamate-γ-semialdehyde (GSAL) in a reversible non-enzymatic reaction. Proline is synthesized from glutamate or ornithine through GSAL/P5C, which is reduced to proline by P5C reductase (PYCR) in a NAD(P)H-dependent reaction. The degradation of proline occurs in the mitochondrion and involves two oxidative steps catalyzed by proline dehydrogenase (PRODH) and GSAL dehydrogenase (GSALDH). PRODH is a flavin-dependent enzyme that couples proline oxidation with reduction of membrane-bound quinone, while GSALDH catalyzes the NAD+-dependent oxidation of GSAL to glutamate. PRODH and PYCR form a metabolic relationship known as the proline-P5C cycle, a novel pathway that impacts cellular growth and death pathways. The proline-P5C cycle has been implicated in supporting ATP production, protein and nucleotide synthesis, anaplerosis, and redox homeostasis in cancer cells. This Perspective details the structures and reaction mechanisms of PRODH and PYCR and the role of the proline-P5C cycle in cancer metabolism. A major challenge in the field is to discover inhibitors that specifically target PRODH and PYCR isoforms for use as tools for studying proline metabolism and the functions of the proline-P5C cycle in cancer. These molecular probes could also serve as lead compounds in cancer drug discovery targeting the proline-P5C cycle.

Redox Modulation of NQO1

NQO1 is a FAD containing NAD(P)H‐dependent oxidoreductase that catalyzes the reduction of quinones and related substrates. In cells, NQO1 participates in a number of binding interactions with other proteins and mRNA and these interactions may be influenced by the concentrations of reduced pyridine nucleotides. NAD(P)H can protect NQO1 from proteolytic digestion suggesting that binding of reduced pyridine nucleotides results in a change in NQO1 structure. We have used purified NQO1 to demonstrate the addition of NAD(P)H induces a change in the structure of NQO1; this results in the loss of immunoreactivity to antibodies that bind to the C‐terminal domain and to helix 7 of the catalytic core domain. Under normal cellular conditions NQO1 is not immunoprecipitated by these antibodies, however, following treatment with β‐lapachone which caused rapid oxidation of NAD(P)H, NQO1 could be readily pulled‐down. Similarly, immunostaining for NQO1 was significantly increased in cells following treatment with β‐lapachone demonstrating that under non‐denaturing conditions the immunoreactivity of NQO1 is reflective of the NAD(P)+/NAD(P)H ratio. In untreated human cells, regions with high intensity immunostaining for NQO1 co‐localize with acetyl α‐tubulin and the NAD+‐dependent deacetylase Sirt2 on the centrosome(s), the mitotic spindle and midbody during cell division. These data provide evidence that during the centriole duplication cycle, NQO1 may provide NAD+ for Sirt2‐mediated deacetylation of microtubules. Overall, the data suggest that NQO1 can act as a redox‐dependent switch where the protein responds to the NAD(P)+/NAD(P)H redox environment by altering its structure promoting the binding or dissociation of NQO1 with target macromolecules.Support or Funding InformationThis work was supported by NIH/NDDK grant 1R01DK109964‐01A.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.