E. Hasegawa et al., A DUAL EFFECT OF 1-METHYL-4-PHENYLPYRIDINIUM (MPP(-ANALOGS ON THE RESPIRATORY-CHAIN OF BOVINE HEART-MITOCHONDRIA())), Archives of biochemistry and biophysics, 337(1), 1997, pp. 69-74
We examined effects of several compounds, structurally related to 1-me
thyl-4-phenylpyridinium (MPP(+)), on the NADH-dependent respiration of
bovine heart submitochondrial particles, 1-Methyl-4-(3'-trimethylammo
niophenyl)pyridinium (analog 8) as well as MPP(+) completely inhibited
O-2 consumption, reduction of ubiquinone-10, and reduction of cytochr
ome b in a dose-dependent manner. The production of superoxide (O-2(-)
) induced by MPP(+) or analog 8 was to the same extent as that by rote
none, an inhibitor of complex I of the mitochondrial respiratory chain
. Rotenone had no additive effect on the maximal production of O-2(-)
induced by MPP(+) or analog 8, suggesting that the production was medi
ated by the same way as rotenone, 1-Methyl-4-(4'-nitrophenyl) pyridini
um (analog 1) induced about 20-fold more production of O-2(-) than MPP
(+) and the production was additively increased by rotenone, Analog 1
only partially inhibited rotenone-sensitive O-2 consumption, Paraquat
induced the production of O-2(-) as much as analog 1, Paraquat, howeve
r, did not inhibit rotenone sensitive O-2 consumption or reduction of
cytochrome b, These results suggest that MPP(+) and its analogs intera
ct with the mitochondrial respiratory chain at two sites, the substrat
e side of the rotenone-binding site and the rotenone-binding site. The
analogs may be reduced to produce O-2(-) at the former site and inhib
it the respiratory chain at the latter site. (C) 1997 Academic Press,
Inc.