The effect of 1-methyl-isoquinoline (MIQ+) on the respiratory inhibition and the uptake of MIQ+ were measured using mouse liver mitochondria. MIQ+ inhibited the electron transport of complex I but did not inhibit the respiration of mitochondria with succinate as a substrate. MIQ+ was taken up by mitochondria in an energy dependent process. Tetraphenylboron enhanced the MIQ+ uptake by mitochondria and its inhibitory effect on respiration. The respiratory inhibition of mitochondria by MIQ+ resulted in release of MIQ+ from mitochondria in medium containing glutamate and malate. These characteristics of MIQ+, for uptake into mitochondria and respiratory inhibition, were similar to those of 1-methyl-4-phenylpyridine (MPP+). The IC50 of MIQ+ for respiratory inhibition was higher than that of MPP+, and the amount of MIQ+ uptake by mitochondria was smaller that of MPP+. The lower ability of MIQ+ for respiratory inhibition as compared to that of MPP+ must result from the lower lipophilic ability of MIQ+ than that of MPP+. These results show that, unlike MPP+, MIQ+ cannot act as a rapid neurotoxin. But, it does not eliminate the possibility that MIQ+ acts as a neurotoxin in the long-term, since MIQ+ was taken up in mitochondria and inhibited the respiration.
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