Evidence that the blockade of mitochondrial respiration by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) involves binding at the same site as the respiratory inhibitor, rotenone

Matthew J. Krueger*, Thomas P. Singer, John E. Casida, Rona R. Ramsay

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

It has been postulated that 1-methyl-4-phenylpyridinium (MPP+) blocks mitochondrial respiration by combining at the same site as rotenone, a potent inhibitor of NADH oxidation in mitochondria, known to act at the junction of NADH dehydrogenase and coenzyme Q (CoQ). The present experiments show that MPP+ and two of its analogs indeed act in a concentration dependent manner to prevent the binding of [14C]-rotenone to submitochondrial particles (ETP) and significantly decrease the inhibition of electron transport caused by rotenone. It therefore appears that MPP+ binds at the same site as rotenone or an adjacent site, supporting the hypothesis that its neurotoxic action is due to the inhibition of mitochondrial respiration.

Original languageEnglish
Pages (from-to)123-128
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume169
Issue number1
DOIs
Publication statusPublished - 31 May 1990

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