The mitochondrial creatine phosphokinase is associated with inner membrane cardiolipin.

Abstract

Inorganic phosphate (Pi) and negatively charged SH-group reagents solubilize the membrane bound mitochondrial creatine phosphokinase (m-CPK) into the medium (1,2). The rebinding of the solubilized m-CPK to the inner mitochondrial membrane is inhibited by adriamycin, a drug widely used in cancer chemotherapy, (3). Adriamycin binds specifically to mitochondrial cardiolipin (4,5) and has been found to inhibit the activity of cardiolipin-dependent proteins, such as cytochrome c oxidase and the phosphate transport protein (6–8). It has been proposed that m-CPK and the ADP/ATP translocator form a tightly coupled functional complex (9,10). The proposal, however, is not universally accepted (11). In this report we present evidence that m-CPK binds to membrane-associated cardiolipin in a reaction that is inhibited by adriamycin in mitochondria as well as in liposomes.