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

doi:10.1016/0006-291X(90)91442-U

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 journal › Article › peer-review

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 language	English
Pages (from-to)	123-128
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	169
Issue number	1
DOIs	https://doi.org/10.1016/0006-291X(90)91442-U
Publication status	Published - 31 May 1990

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@article{9407be9a3b6f4f06bbf2a9537581c62f,

title = "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",

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.",

author = "Krueger, \{Matthew J.\} and Singer, \{Thomas P.\} and Casida, \{John E.\} and Ramsay, \{Rona R.\}",

year = "1990",

month = may,

day = "31",

doi = "10.1016/0006-291X(90)91442-U",

language = "English",

volume = "169",

pages = "123--128",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier",

number = "1",

}

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. / Krueger, Matthew J.; Singer, Thomas P.; Casida, John E. et al.
In: Biochemical and Biophysical Research Communications, Vol. 169, No. 1, 31.05.1990, p. 123-128.

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

TY - JOUR

T1 - 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

AU - Krueger, Matthew J.

AU - Singer, Thomas P.

AU - Casida, John E.

AU - Ramsay, Rona R.

PY - 1990/5/31

Y1 - 1990/5/31

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0025296453

U2 - 10.1016/0006-291X(90)91442-U

DO - 10.1016/0006-291X(90)91442-U

M3 - Article

C2 - 2350337

AN - SCOPUS:0025296453

SN - 0006-291X

VL - 169

SP - 123

EP - 128

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

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

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