Reciprocal effects between spermine and Mg2+ on their movements across the mitochondrial membrane

Mg2+ competitively inhibits spermine transport in energized rat liver mitochondria (RLM) and exhibits a Ki of 0.1 mM on the initial rate and an I50 of 0.6 mM on total spermine accumulation after 20 min. Addition of 2 mM Mg2+ after spermine accumulation induces release of the polyamine. In view of the fact that spermine cycles across the inner membrane under physiological conditions, these results demonstrate that Mg2+ inhibits spermine influx but does not affect the efflux pathway of the polyamine; the inhibitory effect occurs via an interaction with the specific site responsible for spermine transport. Instead, spermine inhibits Mg2+ binding without affecting the rate of Mg2+ transport, suggesting that both cations bind to the same site, which, however, is not used for Mg2+ transport. Spermine also inhibits Mg2+ efflux from RLM induced under conditions of the “low conductance state,” a preliminary step preceding permeability transition pore opening.