Mitochondrial Creatine Kinase (Mi-CK) Forms Octameric Molecules: Structure-Function Relationship and Implications for the CP-Shuttle

Abstract

Creatine kinase (CK) transphosphorylates the phosphoryl group of phospho-creatine (CP) to ADP to regenerate ATP, the primary source of energy in living systems. Besides the “cytosolic” brain-type (BB-CK), muscle-type (MM-CK) and heterodimer-type (MB-CK) isoforms (for review see: Eppenberger et al. 1983), a fourth isoform of CK, the mitochondrial Mi-CK (Jacobs et al. 1984), is also present in significant amounts in tissues with sudden high energy demand, e.g., skeletal and cardiac muscle, brain and photoreceptor cells, and spermatozoa. Mi-CK is restricted to mitochondria and seems to be well adapted to generate CP from ATP produced by oxidative phosphorylation within the mitochondrial matrix (Jacobus and Lehninger, 1973). Mi-CK which is bound at the outer side of the inner mitochondrial membrane (Scholte, 1973) is thought to be functionally coupled to the ATP/ADP-translocator (Saks et al. 1980) and was found to be clearly different in amino acid composition, cDNA sequence and immunological properties from B- and M-CK (Hossle et al. 1988; Schlegel et al. 1988), but conflicting reports on its oligomeric structure (subunit M_r = 43′000) have been published. A mild and efficient scheme for the purification of Mi-CK from chicken cardiac and brain mitochondria was developed which allows the fast isolation of 5–10 mg quantities of the enzyme with a purity of ≥ 99.5% (Schlegel et al. 1988).

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