Mitochondrial creatine kinase interaction with phospholipid vesicles.
The characteristics of the interaction of mitochondrial creatine kinase (mt-CK) with phospholipid vesicles are determined. The presence of negatively charged phospholipids is required to obtain a significant binding of mt-CK. The interaction seems to be largely of an electrostatic nature: it increases with increasing amounts of anionic phospholipid in liposomes and decreases when the ionic strength increases or when the pH of the medium is higher than the pI of mt-CK. We have compared the effects of various effectors used to solubilize mt-CK from the mitochondrial membrane on the binding of mt-CK to liposomes: the nucleotide substrates ATP and ADP have no influence, parahydroxymercuribenzoate, a negatively charged organomercurial compound, partially decreases mt-CK binding; and the anticancer agent adriamycin efficiently prevents mt-CK binding. As monitored by the increase in absorbance, mt-CK causes vesicle aggregation. A differential scanning calorimetry study, using dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol vesicles, shows that mt-CK produces a decrease in the enthalpy variation without any change in the position of the calorimetric peak maximum. This suggests a partial disorganization of the phospholipid bilayer upon interaction with mt-CK.
Vacheron
M J
MJ
UPRESA 5013 CNRS-LYON I Biomembranes et Enzymes Associés, Université Claude Bernard Lyon I, Villeurbanne, France. Vacheron@univ-lyon1.fr
Clottes
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Chautard
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Vial
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D000327:Adsorption / Q000187:drug effects; D000818:Animals; D000838:Anions / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000378:metabolism; D003402:Creatine Kinase / Q000302:isolation & purification / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011107:Polylysine / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology; D012995:Solubility; D013552:Swine; D013816:Thermodynamics
D000838:Anions; D000970:Antineoplastic Agents; D006902:Hydroxymercuribenzoates; D008081:Liposomes; D010743:Phospholipids; C030601:4-hydroxymercuribenzoate; D011107:Polylysine; D012965:Sodium Chloride; D004317:Doxorubicin; D003402:Creatine Kinase