Enhancement of the uptake of 1-methyl-4-phenylpyridinium ion (MPP+) in mitochondria by tetraphenylboron.
The uptake of 1-methyl-4-phenylpyridinium (MPP+) by intact mitochondria was measured by an electrode sensitive to MPP+. The electrode was constructed with a polyvinyl chloride membrane that contained tetraphenylboron (TPB) as an ion-exchange. MPP+ was taken up by mitochondria in an energy-dependent process. TPB rapidly enhanced MPP+ uptake by mitochondria, and then induced release of MPP+ from mitochondria in medium containing glutamate and malate. No release of MPP+ from mitochondria after addition of TPB could be observed in medium containing succinate, the oxidation of which is not inhibited by MPP+. The release of MPP+ was caused by respiratory inhibition by MPP+ taken up in mitochondria. Since the release of MPP+ did not increased O2 uptake in mitochondria, the major part of MPP+ released from the matrix, where no respiratory enzyme inhibited by MPP+ exists. We concluded the following effect of TPB on MPP+ uptake from the results: (1) The increase of MPP+ concentration in matrix by addition of TPB increased the amount of bound to the inner membranes of mitochondria. (2) The increase of the amount of MPP+ in the inner membranes enhanced the respiratory inhibition. (3) The respiratory inhibition induced to release MPP+ from the matrix. The relation between MPP+ distribution in the membrane of mitochondria and the respiratory inhibition by MPP+ are discussed.
Aiuchi
T
T
Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Syou
M
M
Matsunaga
M
M
Kinemuchi
H
H
Nakaya
K
K
Nakamura
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000818:Animals; D004566:Electrodes; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D013775:Tetraphenylborate / Q000494:pharmacology*
D013775:Tetraphenylborate; D015655:1-Methyl-4-phenylpyridinium