Inhibition of mitochondrial electron transport by piericidin A and related compounds

Jeng, Miji; Hall, Carole; Crane, F.L.; Takahashi, Nobutaka; Tamura, Saburo; Folkers, Karl

doi:10.1021/bi00844a010

Cited by 67 publications

(19 citation statements)

References 10 publications

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“…Piericidin and its derivatives are known as potent inhibitors of NADH-ubiquinone oxidoreductase, and piericidin A1 inhibits both mitochondrial and bacterial NADHubiquinone oxidoreductases [21]. The antimicrobial activities (MICs) of piericidin A1 and 3'-rhamnopiericidin A1 previously reported on certain strains (Staphylococcus aureus FDA 209P, Bacillus subtilis ATCC 6633, Escherichia coli NIHJ, Klebsiella pneumoniae ATCC 29655, P. aeruginosa IFO 13725, and Aspergillus oryzae IFO 4221) [22] were more than 100 µg·mL 1 .…”

Section: Discussionmentioning

confidence: 99%

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Piericidins, Novel Quorum-Sensing Inhibitors against Chromobacterium violaceum CV026, from Streptomyces sp. TOHO-Y209 and TOHO-O348

Ooka¹,

Fukumoto²,

Yamanaka³

et al. 2013

OJMC

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Piericidin A1, 3'-rhamnopiericidin A1, and a novel compound piericidin E, a new quorum-sensing (QS) inhibitor against Chromobacterium violaceum CV026, were isolated from the culture broth of Streptomyces sp. QS is well known as a microbial signaling system and controls certain types of gene expression resulting in bioluminescence, biofilm formation, swarming motility, antibiotic biosynthesis, and virulence factor production. C. violaceum CV026 is commonly used to determine qualitative and quantitative QS activity. The structures of piericidin derivatives were characterized, and their QS activities were determined.

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Section: Discussionmentioning

confidence: 99%

“…Compounds 209-2 and 348-2 were found to possess the same structure and were characterized as piericidin A1 (Figure 3) [21,22]. Compound 348-1 was found to be the derivative of piericidin A1and was characterized as 3'-rhamnopiericidin A1 (Figure 4) [23].…”

Section: Structure Elucidationmentioning

confidence: 97%

Piericidins, Novel Quorum-Sensing Inhibitors against Chromobacterium violaceum CV026, from Streptomyces sp. TOHO-Y209 and TOHO-O348

Ooka¹,

Fukumoto²,

Yamanaka³

et al. 2013

OJMC

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“…I n this study piericidin A, an inhibitor of electron transport in the region of the iron-sulphur proteins of the NADH dehydrogenase [22] has been employed to investigate the NADH dehydrogenase responsible for the oxidation of pyridine nucleotide reduced by different substrates. It can be seen from data presented in Fig.6 that piericidin A had no effect on the oxidation of succinate or exogenous NADH and only partially blocked the oxidation of other NAD+-linked substrates.…”

Section: Piericidin a Sensitivity And Location Of The Pyridine-nucleomentioning

confidence: 99%

Pathways for the Oxidation of Malate and Reduced Pyridine Nucleotide by Wheat Mitochondria

Brunton

Palmer

1973

European Journal of Biochemistry

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piericidin A and oxaloacetate have been used as inhibitors to investigate the operation and localisation of NAD+-linked dehydrogenases and the possible compartmentation of these enzymes within the matrix of the mitochondrion. 1.Mitochondria isolated from etiolated shoots of wheat (Triticum vulgare) were shown to oxidise a variety of NAD+-linked substrates. Oxaloacetate, when added to rapidly respiring preparations (i.e. state 3) resulted in a large but transient inhibition ofthe oxidation of both pyruvate and citrate, but had little effect on the rate of oxidation of malate.2. The products of oxidation of malate, in the absence of added NAD+, were found to be a large quantity of pyruvate together with smaller quantities of oxaloacetate and citrate. Using potassium ferricyanide as a non-penetrating electron acceptor it was possible to show that the malate oxidation occurred in the matrix. This is consistent with the operation of both the malic enzyme and a low level of malate dehydrogenase within the matrix of the mitochondrion.3. The low level of inhibition of malate oxidation by oxaloacetate was a function of the concentration of malate and appeared to be of a competitive nature.4. Measurement of the redox state of the endogenous NAD+ pool showed that under phosphorylatig conditions both malate and citrate reduce approximately 15O/, of the total coenzyme. The addition of 0.2 mM oxaloacetate to phosphorylating aerobic mitochondria failed to oxidise any of the NAD+ reduced by malate but resulted in a partial oxidation of NAD+ reduced by citrate. The transition from the aerobic to anaerobic state in the presence of malate resulted in a biphasic reduction of the endogenous NAD+, whereas in the presence of citrate it was monophasic.5 . The oxidation of NAD+-linked substrates, including malate, was found to be only partially inhibited by piercidin A. The piericidin-A-resistant pathway was found to be located internally on the basis of experiments using ferricyanide as a non-penetrating electron acceptor. The first site of phosphorylation was not coupled to oxidation mediated by the piericidin-A-resistant pathway.6. The presence of piericidin A altered the shape of the malate saturation curve. I n the ahsence of the inhibitor it was found to be biphasic; saturating at 60 mM and in its presence to be monophasic saturing a t 15 mM. At high concentrations of malate (60 mM) piericidin A caused approximately a 30 O/, inhibition, similar to that found with other NAD+-linked substrates, while a t lower concentrations of malate (15 mM) piericidin A caused a much higher inhibition (80 O/,), which subsequently recovered to the much higher piericidin-A-resistant rate observed with higher concentrations of malate. 7.I n the presence of piericidin A oxaloacetate caused severe but transient inhibition of malate oxidation, similar in magnitude to that observed during pyruvate oxidation in the absence of piericidin A.8. It was concluded that the data were consistent with the spatial separation of both the internal malic enzyme and ma...

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“…Piericidin A inhibits the oxidative phosphorylation capacity of the NADH oxidase in submitochondrial systems a t concentrations of 30 pmoles/mg protein, that of the succinic oxidase at 6 nmoles/mg protein and the phosphorylation in the cytochrome oxidase region a t concentrations of 5 vmoles/mg protein.…”

mentioning

confidence: 99%

“…Some discrepancies between the piericidin action and the inhibitory action of rotenone and amytal are noted. 6. A hypothesis is put forward for the possible interaction of a non-heme iron component, structurally arranged by S-bonds and coenzyme Q and the relevance of this chelate for the generation of a primary high energy complex.…”

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confidence: 99%

The Effect of Piericidin A on Energy‐Linked Processes in Submitochondrial Particles

Vallin

Löw

1968

European Journal of Biochemistry

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1. Piericidin A inhibits the oxidative phosphorylation capacity of the NADH oxidase in submitochondrial systems a t concentrations of 30 pmoles/mg protein, that of the succinic oxidase at 6 nmoles/mg protein and the phosphorylation in the cytochrome oxidase region a t concentrations of 5 vmoles/mg protein.2. The energy dependent NAD' reductions are 10 times more sensitive to piericidin A than the NADH oxidase reaction. There is a correlation between the oxidation reduction state of the respiratory chain components, presumably of coenzyme Q and the extent of sensivity to the inhibitor.3. Piericidin A and guanidine compounds showed an additive or more than additive inhibitory effect when added together.4. p-Chloromercuribenzoate and piericidin have a synergistic effect when added simultaneously. 2,3-Dimercaptopropanol (BAL) could partly release the piericidin inhibition, in contrast to glutathione, indicating an involvement of proximal -SH-groups in the piericidin sensitive site.5. Some discrepancies between the piericidin action and the inhibitory action of rotenone and amytal are noted.6. A hypothesis is put forward for the possible interaction of a non-heme iron component, structurally arranged by S-bonds and coenzyme Q and the relevance of this chelate for the generation of a primary high energy complex.Piericidin A is an insecticidal metabolite of Streptomyces mobarensis, the chemical structure of which has been determined as a pyridine ring with methoxyl groups, nuclear methyl and hydroxyl groups and an isoprenoid-like side chain arranged in a coenzyme Q like manner [ 1 -31.It acts as a competitive inhibitor of mitochondrial reactions where coenzyme Q is involved [4,5]. This effect, suggested by a similarity in structure between the quinoid coenzyme and the insecticide, was demonstrated as a release of piericidin A inhibited succinic oxidase by the addition of coenzyme Q. It was further shown that NADH oxidase was sensitive to extremely low concentrations of piericidin A.The reduction of cytochrome b after addition of NADH or succinate is considerably delayed in the presence of piericidin A and coenzyme Q reduction is completely abolished (61.

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Inhibition of mitochondrial electron transport by piericidin A and related compounds

Cited by 67 publications

References 10 publications

Piericidins, Novel Quorum-Sensing Inhibitors against Chromobacterium violaceum CV026, from Streptomyces sp. TOHO-Y209 and TOHO-O348

Piericidins, Novel Quorum-Sensing Inhibitors against Chromobacterium violaceum CV026, from Streptomyces sp. TOHO-Y209 and TOHO-O348

Pathways for the Oxidation of Malate and Reduced Pyridine Nucleotide by Wheat Mitochondria

The Effect of Piericidin A on Energy‐Linked Processes in Submitochondrial Particles

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