Dissociation between effects of polyamines on mitochondrial calcium uptake and mitochondrial permeability transition by elongation of polyamine methylene backbone.

The aliphatic polyamine bis(hexamethylene)triamine, a spermidine analogue, was found to lack the enhancing effect on mitochondrial Ca(2+) accumulation which is typical for the natural polyamines, spermidine and spermine. However, like spermine and spermidine, this compound had a significant inhibitory effect on the Ca(2+) and Pi-induced mitochondrial permeability transition. By chromatographic determination of the amount of polyamines bound to mitochondria after a 2 min incubation, it was found that the binding affinity was spermine > or = bis(hexamethylene)triamine > spermidine. There was no competition between binding of spermine and of bis(hexamethylene)triamine. It is concluded that membrane binding sites of bis(hexamethylene)triamine are different from those of spermine. This different membrane interaction is apparently caused by the elongated hydrophobic spans in bis(hexamethylene)triamine and leads to a loss of the effect on Ca(2+) uptake but leaves intact the inhibitory effect on membrane permeability transition.