Quantitative Correlation between the Proton-carrying and Respiratory-stimulating Properties of Uncoupling Agents using Rat Liver Mitochondria

Cunarro, Julia; Weiner, Michael W.

doi:10.1038/245036a0

Cited by 25 publications

(3 citation statements)

References 15 publications

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“…The experiments of Cunarro and Weiner (1973) provide perhaps the most convincing demonstration that there is a direct correlation between the ability of a weak acid to act as an uncoupler of oxidative phosphorylation and the ability of the weak acid to facilitate a passive flux of H + across a mitochondrial membrane. Utilizing poisoned mitochondria as their artificial system, they argued that the swelling induced in such mitochondria by uncouplers was a measure of net proton transport.…”

Section: Relevance Of This Study To the Mitochondriamentioning

confidence: 96%

Complexes between uncouplers of oxidative phosphorylation

Foster

McLaughlin

1974

J. Membrain Biol.

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Summary. We have examined the effects of two weak acid uncouplers of oxidative phosphorylation, 2,4-dinitrophenol and 5,6-dichloro-2-trifluoromethyl-benzimidazole, on the electrical properties of phospholipid bilayer membranes. All the effects they produce are consistent with the charged permeant species being a HA~ complex formed between the neutral acid HA and its anion A-and the current in the aqueous phases being carried by buffered hydrogen ions. When both uncouplers are present simultaneously, all the evidence we have obtained is consistent with the charged permeant species being a HAB-complex formed between the neutral acid HA of one uncoupler and the anion B-of the other. It was necessary, however, to take into account interracial processes and the unstirred layers adjacent to the membrane, the adsorption of anions to the bilayer and the buffer level in the aqueous phases to explain the results in terms of this model. The degree to which these factors will complicate a comparison of results obtained on artificial systems and mitochondria is also discussed.The chemiosmotic hypothesis (

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Section: Relevance Of This Study To the Mitochondriamentioning

confidence: 96%

Complexes between uncouplers of oxidative phosphorylation

Foster

McLaughlin

1974

J. Membrain Biol.

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“…In addition, there is no doubt that the uncoupling effect of gramicidin A is mediated by the formation of a proton channel and induction of proton leakage in the inner mitochondrial membrane. The Mitchell theory puts emphasis not on the P-vs-U correlation but on the correlation between mitochondrial uncoupling (i.e., stimulation of respiration and ATP hydrolysis) and the protonophore activity of uncouplers, which is measured directly in mitochondria [ 61 ]. In the Mitchell theory, it is not important whether the uncoupler induces a proton current in the mitochondrial membrane via the lipid parts of the membrane or via some mitochondrial protein.…”

Section: Interaction Between Protonophores and Mitochondrial Membrane...mentioning

confidence: 99%

Fifty Years of Research on Protonophores: Mitochondrial Uncoupling As a Basis for Therapeutic Action

Kotova

Antonenko

2022

Acta Naturae

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Protonophores are compounds capable of electrogenic transport of protons across membranes. Protonophores have been intensively studied over the past 50 years owing to their ability to uncouple oxidation and phosphorylation in mitochondria and chloroplasts. The action mechanism of classical uncouplers, such as DNP and CCCP, in mitochondria is believed to be related to their protonophoric activity; i.e., their ability to transfer protons across the lipid part of the mitochondrial membrane. Given the recently revealed deviations in the correlation between the protonophoric activity of some uncouplers and their ability to stimulate mitochondrial respiration, this review addresses the involvement of some proteins of the inner mitochondrial membrane, such as the ATP/ADP antiporter, dicarboxylate carrier, and ATPase, in the uncoupling process. However, these deviations do not contradict the Mitchell theory but point to a more complex nature of the interaction of DNP, CCCP, and other uncouplers with mitochondrial membranes. Therefore, a detailed investigation of the action mechanism of uncouplers is required for a more successful pharmacological use, including their antibacterial, antiviral, anticancer, as well as cardio-, neuro-, and nephroprotective effects.

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“…Uncoupling agents disturb transport function by dissipating the proton gradient which in turn destroys the proton motive force (11). It is thought that the uncouplers of oxidative phosphorylation act as proton conductors by dissolving in the membrane and circulating as proton carriers (4,8,16). However, disagreement exists on the interpretation of the role of uncouplers as strictly proton conductors (1,3,31,38).…”

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confidence: 99%

Separation of phenylalanine transport events by using selective inhibitors, and identification of a specific uncoupler activity in Yersinia pestis

Smith¹,

Montie²

1975

J Bacteriol

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Phenylalanine transport in Yersinia pestis TJW was differentially inhibited by sulfhydryl blocking reagents, uncoupling agents, and respiratory inhibitors. Kinetic studies with potassium cyanide and sodium azide showed that these compounds have no immediate effect on the initial rate of phenylalanine transport, but have an immediate and severe inhibitory effect on the rate of oxygen uptake. Identical studies with p-chloromercuribenzoate (pCMB) and 2,4-dinitrophenol (DNP) showed that these compounds have an instantaneous

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Quantitative Correlation between the Proton-carrying and Respiratory-stimulating Properties of Uncoupling Agents using Rat Liver Mitochondria

Cited by 25 publications

References 15 publications

Complexes between uncouplers of oxidative phosphorylation

Complexes between uncouplers of oxidative phosphorylation

Fifty Years of Research on Protonophores: Mitochondrial Uncoupling As a Basis for Therapeutic Action

Separation of phenylalanine transport events by using selective inhibitors, and identification of a specific uncoupler activity in Yersinia pestis

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