A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-Analogs on the respiratory chain of bovine heart mitochondria

Eiji Hasegawa, Dongchon Kang, Kei Sakamoto, Atsushi Mitsumoto, Tetsuo Nagano, Shigeki Minakami, Koichiro Takeshige

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We examined effects of several compounds, structurally related to 1- methyl-4-phenylpyridinium (MPP+), on the NADH-dependent respiration of bovine heart submitochondrial particles. 1-Methyl-4-(3'- trimethylammoniophenyl)pyridinium (analog 8) as well as MPP+ completely inhibited O2 consumption, reduction of ubiquinone-10, and reduction of cytochrome b in a dose-dependent manner. The production of superoxide (O2) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Rotenone had no additive effect on the maximal production of O2 induced by MPP+ or analog 8, suggesting that the production was mediated by the same way as rotenone. 1-Methyl-4-(4'-nitrophenyl) pyridinium (analog 1) induced about 20- fold more production of O2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenonesensitive O2 consumption. Paraquat induced the production of O2 as much as analog 1. Paraquat, however, did not inhibit rotenone-sensitive O2 consumption or reduction of cytochrome b. These results suggest that MPP+ and its analogs interact with the mitochondrial respiratory chain at two sites, the substrate side of the rotenonebinding site and the rotenone-binding site. The analogs may be reduced to produce O2 at the former site and inhibit the respiratory chain at the latter site.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume337
Issue number1
DOIs
Publication statusPublished - Jan 1 1997

Fingerprint

1-Methyl-4-phenylpyridinium
Rotenone
Heart Mitochondria
Mitochondria
Electron Transport
Paraquat
Cytochromes b
Submitochondrial Particles
Superoxides
NAD
Respiration
Binding Sites
Substrates

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-Analogs on the respiratory chain of bovine heart mitochondria. / Hasegawa, Eiji; Kang, Dongchon; Sakamoto, Kei; Mitsumoto, Atsushi; Nagano, Tetsuo; Minakami, Shigeki; Takeshige, Koichiro.

In: Archives of Biochemistry and Biophysics, Vol. 337, No. 1, 01.01.1997, p. 69-74.

Research output: Contribution to journalArticle

Hasegawa, Eiji ; Kang, Dongchon ; Sakamoto, Kei ; Mitsumoto, Atsushi ; Nagano, Tetsuo ; Minakami, Shigeki ; Takeshige, Koichiro. / A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-Analogs on the respiratory chain of bovine heart mitochondria. In: Archives of Biochemistry and Biophysics. 1997 ; Vol. 337, No. 1. pp. 69-74.
@article{915b0e038148435c89741ee894c9b794,
title = "A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-Analogs on the respiratory chain of bovine heart mitochondria",
abstract = "We examined effects of several compounds, structurally related to 1- methyl-4-phenylpyridinium (MPP+), on the NADH-dependent respiration of bovine heart submitochondrial particles. 1-Methyl-4-(3'- trimethylammoniophenyl)pyridinium (analog 8) as well as MPP+ completely inhibited O2 consumption, reduction of ubiquinone-10, and reduction of cytochrome b in a dose-dependent manner. The production of superoxide (O2) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Rotenone had no additive effect on the maximal production of O2 induced by MPP+ or analog 8, suggesting that the production was mediated by the same way as rotenone. 1-Methyl-4-(4'-nitrophenyl) pyridinium (analog 1) induced about 20- fold more production of O2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenonesensitive O2 consumption. Paraquat induced the production of O2 as much as analog 1. Paraquat, however, did not inhibit rotenone-sensitive O2 consumption or reduction of cytochrome b. These results suggest that MPP+ and its analogs interact with the mitochondrial respiratory chain at two sites, the substrate side of the rotenonebinding site and the rotenone-binding site. The analogs may be reduced to produce O2 at the former site and inhibit the respiratory chain at the latter site.",
author = "Eiji Hasegawa and Dongchon Kang and Kei Sakamoto and Atsushi Mitsumoto and Tetsuo Nagano and Shigeki Minakami and Koichiro Takeshige",
year = "1997",
month = "1",
day = "1",
doi = "10.1006/abbi.1996.9726",
language = "English",
volume = "337",
pages = "69--74",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-Analogs on the respiratory chain of bovine heart mitochondria

AU - Hasegawa, Eiji

AU - Kang, Dongchon

AU - Sakamoto, Kei

AU - Mitsumoto, Atsushi

AU - Nagano, Tetsuo

AU - Minakami, Shigeki

AU - Takeshige, Koichiro

PY - 1997/1/1

Y1 - 1997/1/1

N2 - We examined effects of several compounds, structurally related to 1- methyl-4-phenylpyridinium (MPP+), on the NADH-dependent respiration of bovine heart submitochondrial particles. 1-Methyl-4-(3'- trimethylammoniophenyl)pyridinium (analog 8) as well as MPP+ completely inhibited O2 consumption, reduction of ubiquinone-10, and reduction of cytochrome b in a dose-dependent manner. The production of superoxide (O2) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Rotenone had no additive effect on the maximal production of O2 induced by MPP+ or analog 8, suggesting that the production was mediated by the same way as rotenone. 1-Methyl-4-(4'-nitrophenyl) pyridinium (analog 1) induced about 20- fold more production of O2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenonesensitive O2 consumption. Paraquat induced the production of O2 as much as analog 1. Paraquat, however, did not inhibit rotenone-sensitive O2 consumption or reduction of cytochrome b. These results suggest that MPP+ and its analogs interact with the mitochondrial respiratory chain at two sites, the substrate side of the rotenonebinding site and the rotenone-binding site. The analogs may be reduced to produce O2 at the former site and inhibit the respiratory chain at the latter site.

AB - We examined effects of several compounds, structurally related to 1- methyl-4-phenylpyridinium (MPP+), on the NADH-dependent respiration of bovine heart submitochondrial particles. 1-Methyl-4-(3'- trimethylammoniophenyl)pyridinium (analog 8) as well as MPP+ completely inhibited O2 consumption, reduction of ubiquinone-10, and reduction of cytochrome b in a dose-dependent manner. The production of superoxide (O2) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Rotenone had no additive effect on the maximal production of O2 induced by MPP+ or analog 8, suggesting that the production was mediated by the same way as rotenone. 1-Methyl-4-(4'-nitrophenyl) pyridinium (analog 1) induced about 20- fold more production of O2 than MPP+ and the production was additively increased by rotenone. Analog 1 only partially inhibited rotenonesensitive O2 consumption. Paraquat induced the production of O2 as much as analog 1. Paraquat, however, did not inhibit rotenone-sensitive O2 consumption or reduction of cytochrome b. These results suggest that MPP+ and its analogs interact with the mitochondrial respiratory chain at two sites, the substrate side of the rotenonebinding site and the rotenone-binding site. The analogs may be reduced to produce O2 at the former site and inhibit the respiratory chain at the latter site.

UR - http://www.scopus.com/inward/record.url?scp=0030990293&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030990293&partnerID=8YFLogxK

U2 - 10.1006/abbi.1996.9726

DO - 10.1006/abbi.1996.9726

M3 - Article

C2 - 9395404

AN - SCOPUS:0030990293

VL - 337

SP - 69

EP - 74

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 1

ER -