Isolation of an electrogenic K+/Ca2+ ionophore from an ionophoroprotein of beef heart mitochondria.

Abstract

A K+/Ca2+ electrogenic ionophore has been isolated from an ionophoroprotein of beef heart mitochondria and identified as a neutral peptide of molecular weight 1600. The amino acid composition and cationic specificity of the ionophore have been determined. The free ionophore was released from the ionophoroprotein as a consequence of tryptic digestion. The ionophoroprotein can be converted to an ionophoropeptide (molecular weight 5100) by proteolysis without release of the free ionophore. The isolation of a K+/Ca2+ ionophore thus provides an introduction to the general technology of extracting ionophoroproteins and of releasing ionophores from these proteins by proteolytic digestion. Blondin and Green (1) have invoked direct coupling as the principle underlying mitochondrial energy coupling; the paired moving charge model translates that principle (1-3). A crucial prediction of the model is a major commitment of the inner mitochondrial membrane to ionophore-mediated coupled processes. The following experimental studies have fully confirmed this commitment: (a) intrinsic ionophores have been implicated in the mechanism of uncoupling (4); (b) energy coupling in cytochrome oxidase has been shown to depend upon the electrostatic interaction of an electron in the electron transfer complex with a positively charged ionophoric species in the ionophore transfer complex intrinsic to the oxidase (5); (c) the activation of Pi and ADP-the critical processes in coupled ATP synthesis and hydrolysis-have been shown to be ionophore-mediated and cation-dependent (R. J. Kessler, H.

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“…An electrogenic K÷/Ca 2÷ ionophore from beef-heart mitochondria was characterized as a neutral peptide of mol. wt 1600 [14]. Peptides have been shown to have the ability to bind metal ions [15].…”