Myxothiazol, a new inhibitor of the cytochrome b-c1 segment of the respiratory chain

Thierbach, Georg; Reichenbach, Hans

doi:10.1016/0005-2728(81)90238-3

Cited by 223 publications

(89 citation statements)

References 19 publications

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“…antimycin A could be attributed to an effect on chloroplasts or mitochondria, we used myxothiazol, another cytochrome bc 1 inhibitor that inhibits the mitochondrial complex by interacting with cytochrome b at a different site (von Jagow and Engel, 1981;Thierbach and Reichenbach, 1981). We found that, in contrast to the effect of antimycin A, myxothiazol had no significant effect on qP and a slight inhibitory effect on qN induction curves, this effect being similar in WT and ndhB Ϫ (Fig.…”

Section: Resultsmentioning

confidence: 79%

Increased Sensitivity of Photosynthesis to Antimycin A Induced by Inactivation of the Chloroplast ndhB Gene. Evidence for a Participation of the NADH-Dehydrogenase Complex to Cyclic Electron Flow around Photosystem I

et al. 2001

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) were used to study the role of the NADH-dehydrogenase complex (NDH) during photosynthesis and particularly the involvement of this complex in cyclic electron flow around photosystem I (PSI). Photosynthetic activity was determined on leaf discs by measuring CO 2 exchange and chlorophyll fluorescence quenchings during a dark-to-light transition. In the absence of treatment, both non-photochemical and photochemical fluorescence quenchings were similar in ndhB Ϫ and wild type (WT). When leaf discs were treated with 5 m antimycin A, an inhibitor of cyclic electron flow around PSI, both quenchings were strongly affected. At steady state, maximum photosynthetic electron transport activity was inhibited by 20% in WT and by 50% in ndhB Ϫ . Under non-photorespiratory conditions (2% O 2 , 2,500 L L Ϫ1 CO 2 ), antimycin A had no effect on photosynthetic activity of WT, whereas a 30% inhibition was observed both on quantum yield of photosynthesis assayed by chlorophyll fluorescence and on CO 2 assimilation in ndhB Ϫ . The effect of antimycin A on ndhB Ϫ could not be mimicked by myxothiazol, an inhibitor of the mitochondrial cytochrome bc 1 complex, therefore showing that it is not related to an inhibition of the mitochondrial electron transport chain but rather to an inhibition of cyclic electron flow around PSI. We conclude to the existence of two different pathways of cyclic electron flow operating around PSI in higher plant chloroplasts. One of these pathways, sensitive to antimycin A, probably involves ferredoxin plastoquinone reductase, whereas the other involves the NDH complex. The absence of visible phenotype in ndhB Ϫ plants under normal conditions is explained by the complement of these two pathways in the supply of extra-ATP for photosynthesis.During oxygenic photosynthesis of C 3 plants, both photosystem II (PSII) and photosystem I (PSI) cooperate to achieve NADP ϩ reduction using water as an electron donor and generate a trans-membrane proton gradient driving ATP synthesis. Although NADP ϩ reduction is recognized to be dependent on the activity of both photosystems through electron transport reactions of the "Z" scheme (Hill and Bendall, 1960;Redding et al., 1999), it has early been reported from studies on isolated thylakoids that ATP could be produced by the sole PSI through cyclic electron transfer reactions (Arnon, 1959). The cyclic electron flow around PSI has been extensively studied in thylakoids and/or chloroplasts of C 3 plants (for review, see Fork and Herbert, 1993; Bendall and Manasse, 1995). This mechanism has been suggested to provide ATP for a variety of cellular processes, including stress adaptation (Havaux et al., 1991) and CO 2 fixation (Furbank and Horton, 1987; Herbert et al., 1990). During photosynthetic CO 2 fixation, both NADPH and ATP are used to regenerate ribulose-1,5-bisphosphate and allow functioning of the photosynthetic carbon reduction cycle (Calvin cycle). In the absence of Q cycle, when one NADPH is produced by linear electron transport reactions, four H ϩ are released in ...

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Section: Resultsmentioning

confidence: 79%

Increased Sensitivity of Photosynthesis to Antimycin A Induced by Inactivation of the Chloroplast ndhB Gene. Evidence for a Participation of the NADH-Dehydrogenase Complex to Cyclic Electron Flow around Photosystem I

et al. 2001

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“…Further isolation procedures were carried out in the same medium without EGTA. 31 Measurements of NADH-oxidation and difference spectra. In both assays, SMP were suspended in 75 mM air saturated sodium potassium phosphate buffer pH 7. in 1,2-dichloroethane (10 mL) was added dropwise, and the mixture was stirred for 2 h at r.t.…”

Section: Methodsmentioning

confidence: 99%

Iromycins from Streptomyces sp. and from synthesis: New inhibitors of the mitochondrial electron transport chain

Surup

Shojaei

Zezschwitz

et al. 2008

Bioorganic & Medicinal Chemistry

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CitationIromycins Abstract:Two new α-pyridone metabolites, iromycin E and F, were isolated from cultures of strain Streptomyces sp. Dra 17, thus expanding the recently discovered iromycin family. Their inhibitory potential on the mitochondrial respiratory chain was examined and revealed that iromycin metabolites block NADH oxidation in beef heart submitochondrial particles with different efficacy, yet remarkably show only very low cytotoxicity. Difference spectroscopic studies indicated that iromycins inhibited the electron transport at the site of complex I (NADH-ubiquinone oxidoreductase). Derivatives of the natural products were semisynthetically prepared and provided detailed insights into structure activity relationships.Drawn from these results, there are strong similarities with the piercidins, which are among the most potent complex I inhibitors of the mitochondrial electron transport chain.Furthermore, total synthesis afforded new analogues, and the non-natural iromycin S (IC 50 = 58 ng/mL) emerged as the most active compound, thus opening avenues of future studies with the iromycins as new valuable biochemical tools.2

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“…To investigate whether the QCR is involved in selenate respiration and could therefore be responsible for electron transfer to the di-heme cytochrome (cytc-Ts4), classic inhibitors of respiratory chains were used during selenate and nitrite respiration. The inhibitors myxothiazol and antimycin A specifically inhibit the QCR, but at different sites (29). Myxothiazol binds to the Q o site on the b heme subunit of QCR.…”

Section: Quinol-cytochrome C Oxidoreductase Is An Electron Donor To Smentioning

confidence: 99%

Quinol-cytochrome c Oxidoreductase and Cytochrome c4 Mediate Electron Transfer during Selenate Respiration in Thauera selenatis

Lowe

Bydder

Hartshorne

et al. 2010

Journal of Biological Chemistry

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Selenate reductase (SER) from Thauera selenatis is a periplasmic enzyme that has been classified as a type II molybdoenzyme. The enzyme comprises three subunits SerABC, where SerC is an unusual b-heme cytochrome. In the present work the spectropotentiometric characterization of the SerC component and the identification of redox partners to SER are reported. The mid-point redox potential of the b-heme was determined by optical titration (E m ؉ 234 ؎ 10 mV). A profile of periplasmic c-type cytochromes expressed in T. selenatis under selenate respiring conditions was undertaken. Two c-type cytochromes were purified (ϳ24 and ϳ6 kDa), and the 24-kDa protein (cytc-Ts4) was shown to donate electrons to SerABC in vitro. Protein sequence of cytc-Ts4 was obtained by N-terminal sequencing and liquid chromatographytandem mass spectrometry analysis, and based upon sequence similarities, was assigned as a member of cytochrome c 4 family. Redox potentiometry, combined with UV-visible spectroscopy, showed that cytc-Ts4 is a diheme cytochrome with a redox potential of ؉282 ؎ 10 mV, and both hemes are predicted to have His-Met ligation. To identify the membrane-bound electron donors to cytcTs4, growth of T. selenatis in the presence of respiratory inhibitors was monitored. The specific quinol-cytochrome c oxidoreductase (QCR) inhibitors myxothiazol and antimycin A partially inhibited selenate respiration, demonstrating that some electron flux is via the QCR. Electron transfer via a QCR and a diheme cytochrome c 4 is a novel route for a member of the DMSO reductase family of molybdoenzymes.Within the DMSO reductase family of type II molybdoenzymes (1) there is a distinct clade of enzymes that are translocated to the periplasm using the twin arginine translocation (TAT) 4 pathway (2, 3) and possess a monomeric b-type heme-containing ␥-subunit (1). The enzymes within this clade function as either dehydrogenases (e.g. ethylbenzene dehydrogenase (EBDH) from Aromatoleum aromaticum (4) and dimethylsulfide dehydrogenase from Rhodovulum sulfidophilum (1, 5)) or reductases (e.g. selenate reductase from Thauera selenatis (6, 7) and chlorate reductase from Ideonella dechloratans (8, 9)) and catalyze either hydride or oxygen transfer as generalized by Reaction 1.These soluble enzymes consist of three subunits and in addition to the b-heme cytochrome (␥-subunit), they comprise an ironsulfur protein (␤-subunit) coordinating 1 ϫ [3Fe-4S] cluster and 3 ϫ [4Fe-4S] clusters, and a catalytic component (␣-subunit) that coordinates a [4Fe-4S] cluster and the active site molybdopterin guanine dinucleotide cofactor (10, 11) (Fig. 1). The reductases play a pivotal function, coupling the reduction of substrates to the generation of the proton-motive force (PMF). Identifying the route by which electrons are transferred to these reductases is vital to understanding their bioenergetics (12). How periplasmic substrate reduction can generate a PMF, which is sufficient to support growth, is of considerable interest. The use of selenate and selenite as bacterial...

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Myxothiazol, a new inhibitor of the cytochrome b-c1 segment of the respiratory chain

Cited by 223 publications

References 19 publications

Increased Sensitivity of Photosynthesis to Antimycin A Induced by Inactivation of the Chloroplast ndhB Gene. Evidence for a Participation of the NADH-Dehydrogenase Complex to Cyclic Electron Flow around Photosystem I

Increased Sensitivity of Photosynthesis to Antimycin A Induced by Inactivation of the Chloroplast ndhB Gene. Evidence for a Participation of the NADH-Dehydrogenase Complex to Cyclic Electron Flow around Photosystem I

Iromycins from Streptomyces sp. and from synthesis: New inhibitors of the mitochondrial electron transport chain

Quinol-cytochrome c Oxidoreductase and Cytochrome c4 Mediate Electron Transfer during Selenate Respiration in Thauera selenatis

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