Enhancement by tetraphenylboron of the interaction of the 1-methyl-4-phenylpyridinium ion (MPP+) with mitochondria

Rona R. Ramsay; Rolf J. Mehlhorn; Thomas P. Singer

doi:10.1016/0006-291X(89)92205-5

Enhancement by tetraphenylboron of the interaction of the 1-methyl-4-phenylpyridinium ion (MPP⁺) with mitochondria

Rona R. Ramsay^*, Rolf J. Mehlhorn, Thomas P. Singer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Inhibition of mitochondrial energy production by MPP⁺ may be the key step in chemically-induced Parkinson's disease. Tetraphenylboron (TPB^-) markedly enhances the effect of MPP⁺. Inhibition of respiration and uptake of MPP⁺ are accelerated, the former by up to two orders of magnitude. TPB^- increases the final concentration of MPP⁺ in the matrix by 2-3 fold, insufficient to explain the rapid inhibition of respiration. TPB^- lowers the membrane surface potential by only about 20%, but increases the partitioning of MPP⁺ into organic solvent by one order of magnitude. TPB^- also enhances the effect of MPP⁺ on inverted membranes, reducing the I₅₀ by an order of magnitude. We suggest that TPB^- acts by ion pairing with MPP⁺ to facilitate penetration into mitochondria as well as access to a hydrophobic inhibition site on NADH dehydrogenase.

Original language	English
Pages (from-to)	983-990
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	159
Issue number	3
DOIs	https://doi.org/10.1016/0006-291X(89)92205-5
Publication status	Published - 31 Mar 1989

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title = "Enhancement by tetraphenylboron of the interaction of the 1-methyl-4-phenylpyridinium ion (MPP+) with mitochondria",

abstract = "Inhibition of mitochondrial energy production by MPP+ may be the key step in chemically-induced Parkinson's disease. Tetraphenylboron (TPB-) markedly enhances the effect of MPP+. Inhibition of respiration and uptake of MPP+ are accelerated, the former by up to two orders of magnitude. TPB- increases the final concentration of MPP+ in the matrix by 2-3 fold, insufficient to explain the rapid inhibition of respiration. TPB- lowers the membrane surface potential by only about 20%, but increases the partitioning of MPP+ into organic solvent by one order of magnitude. TPB- also enhances the effect of MPP+ on inverted membranes, reducing the I50 by an order of magnitude. We suggest that TPB- acts by ion pairing with MPP+ to facilitate penetration into mitochondria as well as access to a hydrophobic inhibition site on NADH dehydrogenase.",

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AU - Ramsay, Rona R.

AU - Mehlhorn, Rolf J.

AU - Singer, Thomas P.

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N2 - Inhibition of mitochondrial energy production by MPP+ may be the key step in chemically-induced Parkinson's disease. Tetraphenylboron (TPB-) markedly enhances the effect of MPP+. Inhibition of respiration and uptake of MPP+ are accelerated, the former by up to two orders of magnitude. TPB- increases the final concentration of MPP+ in the matrix by 2-3 fold, insufficient to explain the rapid inhibition of respiration. TPB- lowers the membrane surface potential by only about 20%, but increases the partitioning of MPP+ into organic solvent by one order of magnitude. TPB- also enhances the effect of MPP+ on inverted membranes, reducing the I50 by an order of magnitude. We suggest that TPB- acts by ion pairing with MPP+ to facilitate penetration into mitochondria as well as access to a hydrophobic inhibition site on NADH dehydrogenase.

AB - Inhibition of mitochondrial energy production by MPP+ may be the key step in chemically-induced Parkinson's disease. Tetraphenylboron (TPB-) markedly enhances the effect of MPP+. Inhibition of respiration and uptake of MPP+ are accelerated, the former by up to two orders of magnitude. TPB- increases the final concentration of MPP+ in the matrix by 2-3 fold, insufficient to explain the rapid inhibition of respiration. TPB- lowers the membrane surface potential by only about 20%, but increases the partitioning of MPP+ into organic solvent by one order of magnitude. TPB- also enhances the effect of MPP+ on inverted membranes, reducing the I50 by an order of magnitude. We suggest that TPB- acts by ion pairing with MPP+ to facilitate penetration into mitochondria as well as access to a hydrophobic inhibition site on NADH dehydrogenase.

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Enhancement by tetraphenylboron of the interaction of the 1-methyl-4-phenylpyridinium ion (MPP⁺) with mitochondria

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