Magnesium-phenethylbiguanide competition in Mg2+-depleted hepatic mitochondria

Guinea pig liver mitochondria 40–70 per cent depleted of magnesium are three times more sensitive to phenethylbiguanide inhibition of state 3 respiration than are comparable controls. Similar results are obtained whether the depletion is accomplished by the divalent cation ionophore A23187 or by incubation with inorganic phosphate. In contrast to controls, inhibition in Mg-depleted mitochondria is competitively reversed by Mg 2+ . These phenomena are observed with NAD + -linked substrates, stimulated by either ADP or Ca 2+ , but not with succinate. The Mg-depleted mitochondria can be restored to the normal degree of phenethylbiguanide sensitivity by incubation with high levels of Mg 2+ followed by washing. As in controls, phenethylbiguanide inhibition in Mg-repleted mitochondria is not reversed by Mg 2+ . These results suggest a dual action of Mg 2+ : (1) a structural role of bound magnesium which regulates the activity of cation transporters, and (2) competition between Mg 2+ in solution and guanidinium derivatives for a cation carrier.