The relation between respiratory inhibition and uptake of 1-methyl-isoquinoline (MIQ +) in mitochondria

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 IC 50 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.