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 journalArticlepeer-review

35 Citations (Scopus)

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 languageEnglish
Pages (from-to)983-990
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume159
Issue number3
DOIs
Publication statusPublished - 31 Mar 1989

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