Mechanism of Action of Reagents that uncouple Oxidative Phosphorylation

Weinbach, Eugene C.; Garbus, Joel

doi:10.1038/2211016a0

Cited by 239 publications

(156 citation statements)

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“…An alternate explanation can be proposed for the bell-shaped curves from the observations summarized by Weinbach and Garbus (28). The MBPUs, like the phenolic types of uncouplers (28), may bind to mitochondrial proteins.…”

Section: Methodsmentioning

confidence: 99%

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Effects of Optically Active 1-(α-Methylbenzyl)-3-(3,4-dichlorophenyl)urea on Reactions of Mitochondria and Chloroplasts

Moreland

Boots

1971

Plant Physiol.

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Effects of the R-and S-isomers and racemate of 1-(amethylbenzyl) -3-(3, 4-dichlorophenyl)urea (MBPU) were measured on phosphorylation and electron transport in mung bean (Phaseolus aureus L.) mitochondria and spinach (Spinacia oleracea L.) chloroplasts.In chloroplasts, S-MBPU inhibited basal and methylamine-uncoupled electron transport with ferricyanide as the oxidant, both photoreduction and coupled photophosphorylation with water as the electron donor and with ferricyanide and nicotinamide adenine dinucleotide phosphate (NADP) as oxidants, and cyclic photophosphorylation with phenazine methosulfate as the electron mediator under an argon gas phase. With ascorbate 2, 6-dichlorophenolindophenol as the electron donor, phosphorylation coupled to NADP reduction was inhibited, but the reduction of NADP was not inhibited. The R -isomer of MBPU, like the S-isomer, inhibited all of the photophosphorylation reactions studied. However, unlike the S-isomer, the Risomer either did not inhibit or was a very weak inhibitor of all photoreduction reactions. The effects of the MBPUs on the chloroplast reactions can be explained by action at two different sites: an optically specific site near photosystem II and the oxygen evolution pathway, and a second optically nonspecific site associated with the generation of ATP.In mitochondria, both the R-and S-isomers stimulated state 4 respiration, inhibited state 3 respiration, and released oligomycin -inhibited respiration with malate, succinate, and NADH as substrates. Both enantiomers were equally active in all studies with malate and succinate as substrates. However, with NADH as substrate, R-MBPU was a stronger inhibitor of state 3 respiration and a weaker stimulator of state 4 respiration than S -MBPU.

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Section: Methodsmentioning

confidence: 99%

“…The MBPUs, like the phenolic types of uncouplers (28), may bind to mitochondrial proteins. Proteins undergo conformational transitions as a consequence of this binding, which could result in structural disorganization and an altered function of the enzymes which catalyze the coupling of phosphorylation to electron transport.…”

Section: Methodsmentioning

confidence: 99%

Effects of Optically Active 1-(α-Methylbenzyl)-3-(3,4-dichlorophenyl)urea on Reactions of Mitochondria and Chloroplasts

Moreland

Boots

1971

Plant Physiol.

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“…(Sanphui et al, 2012, Weinbach & Garbus, 1969 Very recently, it has also been investigated for additional therapeutic applications, including anti-bacterial and anti-tumor activities. (Helfman, 2011, Imperi et al, 2013, Yo et al, 2012 NCL is a BCS class II drug, virtually insoluble in water, and is 2 formulated as a suspension and in chewable tablet form.…”

Section: Introductionmentioning

confidence: 99%

Niclosamide methanol solvate and niclosamide hydrate: structure, solvent inclusion mode and implications for properties

Harriss

Wilson

Evans

2014

Acta Crystallogr C Struct Chem

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This is the accepted version of the following article: Harriss, Bethany and Wilson, Claire and Evans, Ivana R (2014) 'Niclosamide methanol solvate and niclosamide hydrate : structure, solvent inclusion mode and implications for properties.', Acta crystallographica section C : structural chemistry., 70 (8). pp. 758-763 which has been published in nal form at http://dx.doi.org/10.1107/S2053229614015496. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details.

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“…It is not impossible that some of them display side effects associated with their interaction with mitochondrial proteins [28] or other metabolic processes apart from oxidative phosphorylation (e.g. see [29] ).…”

Section: Discussionmentioning

confidence: 99%

Degradation of mitochondrial respiratory system of Saccharomyces cerevisiae, induced by respiratory inhibitors, uncouplers and anaerobiosis

1970

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Mechanism of Action of Reagents that uncouple Oxidative Phosphorylation

Cited by 239 publications

References 46 publications

Effects of Optically Active 1-(α-Methylbenzyl)-3-(3,4-dichlorophenyl)urea on Reactions of Mitochondria and Chloroplasts

Effects of Optically Active 1-(α-Methylbenzyl)-3-(3,4-dichlorophenyl)urea on Reactions of Mitochondria and Chloroplasts

Niclosamide methanol solvate and niclosamide hydrate: structure, solvent inclusion mode and implications for properties

Degradation of mitochondrial respiratory system of Saccharomyces cerevisiae, induced by respiratory inhibitors, uncouplers and anaerobiosis

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