Cardiolipin is the membrane receptor for mitochondrial creatine phosphokinase.

Müller, Michèle; Moser, Rolf; Cheneval, Dominique; Carafoli, Ernesto

doi:10.1016/s0021-9258(19)83700-6

Cited by 136 publications

(9 citation statements)

References 33 publications

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“…On the other hand, pure CL vesicles retained about 84% of the bound protein. These values further support the role of cardiolipin for Mi-CK binding and are in good accordance with literature data proposing that CL is one of the most important receptors because of its high abundance in the inner mitochondrial membrane (Mu ¨ller et al, 1985: Cheneval et al, 1989Rojo et al, 1991a). The high value for the calculated association equilibrium constant K 1 (343.6 for 16% CL vesicles) indicates that in ViVo almost all of the octameric Mi-CK must be bound to the inner membrane.…”

Section: Discussionsupporting

confidence: 89%

“…The cytosolic isoforms are always homo-or heterodimeric (MM-, MB-, or BB-CK), whereas the mitochondrial isoforms of CK also form octamers. Mi-CKs are localized between the inner and outer mitochondrial membrane where they are bound to the cardiolipin-rich inner leaflet (Mu ¨ller et al, 1985) and along the cristae membranes (Wegmann, 1991). The octamer consists of four homodimers (M r (dimer) ) 84 000) displaying a P422 symmetry which gives rise to a cube-shaped molecule (Schnyder et al, 1991).…”

mentioning

confidence: 99%

“…Evidence for a key role of Mi-CK in mitochondrial membrane contact sites in ViVo has been put forward as well (Brdiczka, 1991;Kottke et al, 1991). In addition, it has been shown that Mi-CK is able to interact with porin of the outer mitochondrial membrane (Brdiczka et al, 1994) whereas cardiolipin (CL) has been identified as one possible inner-membrane receptor of Mi-CK (Mu ¨ller et al, 1985). A functional coupling of Mi-CK to the adenine nucleotide translocase (ANT; synonyms: AAC, ADT1) has been demonstrated experimentally with isolated mitochondria and permeabilized cells (Jacobus, 1985;Saks et al, 1985Saks et al, , 1994, indicating that Mi-CK has preferential access to mitochondrial matrix-produced ATP transported by the ANT.…”

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confidence: 99%

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Membrane-Binding and Lipid Vesicle Cross-Linking Kinetics of the Mitochondrial Creatine Kinase Octamer

1996

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Mitochondrial creatine kinase (Mi-CK; EC 2.7.3.2) is a positively charged enzyme located between the mitochondrial inner and outer membrane as well as along the cristae membranes. The octameric form of Mi-CK is able to cross-link membranes to form contact sites. The process of Mi-CK membrane binding and Mi-CK-induced cross-linking of model membrane vesicles containing different amounts of cardiolipin (CL) was investigated in vitro. First, the direct binding of octameric Mi-CK to immobilized lipid vesicles containing cardiolipin was monitored by plasmon resonance (BiaCore). The analysis of the pseudo-first-order on- and off-rate constants indicates that there are two binding sites with different affinity for Mi-CK on the membrane. The association equilibrium constants obtained at 25 degrees C were 813.7 (for 100% CL) and 343.6 (for 16% CL), respectively, for the high-affinity binding mode. Second, the Mi-CK-induced vesicle cross-linking kinetics were analyzed by fixed-angle light scattering. Only octameric Mi-CK induced bridged vesicle/protein complexes, whereas dimeric Mi-CK failed to induce vesicle cross-linking. For vesicles containing 100% cardiolipin, the pseudo-first-order association rate constant was 2.55 x 10(-3) s-1, while for membranes containing 16% cardiolipin and 84% PC a constant of 6.25 x 10(-3) s-1 was found. The examined kinetic properties of the system suggest a two-step model for Mi-CK-induced vesicle cross-linking which consists of a fast binding step of the enzyme to the membrane, followed by a remarkably slower cross-linking reaction between Mi-CK-covered vesicles. The data obtained by in vitro biophysical methods agree with earlier experiments done with mitoplasts and isolated mitochondrial membranes and explain the in vivo accumulation of Mi-CK at contact sites between the inner and outer mitochondrial membrane and the formation of Mi-CK-rich intramitochondrial inclusions observed in creatine-depleted animals as well as in patients with mitochondrial cytopathies.

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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

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confidence: 99%

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Membrane-Binding and Lipid Vesicle Cross-Linking Kinetics of the Mitochondrial Creatine Kinase Octamer

1996

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“…This type of selective interaction is implicit in the proposal of Vick et al (1981) that cardiolipin assists in the binding of cytochrome c to its site of action on the oxidase enzyme. It is also worth noting here that this role for cardiolipin would not be dissimilar to its receptor function for the mitochondrial creatine kinase enzyme as proposed by Müller et al (1985), since this also implies a specific interaction with lipid sites that are segregated from inner membrane bulk components.…”

Section: Methodsmentioning

confidence: 67%

Reversible unfolding of cytochrome c upon interaction with cardiolipin bilayers. I. Evidence from deuterium NMR measurements

Spooner¹,

Watts²

1991

Biochemistry

126

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Deuterium NMR has been used to investigate the structure and dynamic state of cytochrome c complexed with bilayers of cardiolipin. Reductive methylation was employed to prepare [N epsilon, N epsilon-C2H3]lysyl cytochrome c, and deuterium exchange provided labeling of backbone sites to give [amide-2H]cytochrome c or more selective labeling of just histidine residues in [epsilon-2H]histidine cytochrome c. Deuterium NMR measurements on [N epsilon, N epsilon-C2H3]lysyl cytochrome c in the solid state showed restricted motions, fairly typical of the behavior of aliphatic side-chain sites in proteins. The [amide-2H]cytochrome c provided "immobile" amide spectra showing that only the most stable backbone sites remained labeled in this derivative. Relaxation measurements on the aqueous solution of [amide-2H]cytochrome c yielded a rotational correlation time of 7.9 ns for the protein, equivalent to a hydrodynamic diameter of 4.0 nm, just 0.6 nm greater than its largest crystallographic dimension. Similar measurements on [epsilon-2H]histidine cytochrome c in solution showed that all labeled histidine residues were also "immobile" compared with the overall reorientational motion of the protein. The interaction with cardiolipin bilayers appeared to create a high degree of mobility for the side-chain sites of [N epsilon, N epsilon-C2H3]lysyl cytochrome c and perturbed backbone structure to instantaneously release all deuterons in [amide-2H]cytochrome c. The [epsilon-2H]histidine cytochrome c derivative, when complexed with cardiolipin, failed to produce any detectable wide-line 2H NMR spectrum, demonstrating that the overall reorientational motion of bound protein was not isotropic on the NMR time scale, i.e., tau c greater than 10(-7)s.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Cardiolipin, found almost exclusively in the inner mitochondrial membrane and in bacterial membranes, is an acidic phospholipid with two phosphatidyl groups linked via a single glycerol moiety and was the subject of considerable interest in studies on cytochrome c oxidase (Awasthi et al, 1971;Fry et al, 1980;Robinson et al, 1980;Robinson & Wiginton, 1985). This lipid was suggested to influence the catalytic activity of several mitochondrial proteins [see review in Lambeth (1985)] and might serve as a recognition site on the inner mitochondrial membrane for lipid-protein interactions (Muller et al, 1985).…”

mentioning

confidence: 99%

Labeling of bovine heart cytochrome c oxidase with analogs of phospholipids. Synthesis and reactivity of a new cardiolipin benzaldehyde probe

Kuppe¹,

Mrsny²,

Shimizu³

et al. 1987

Biochemistry

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The syntheses of two new radioactive probes derived from cardiolipin and phosphatidylcholine are reported. These probes are derivatives of natural lipids and contain an amine-specific benzaldehyde in the head-group region. This functional group allows a choice of timing of the reaction (e.g., after equilibration and detergent removal) because an irreversible covalent bond is formed only upon the addition of reducing agent. These probes, as well as a benzaldehyde analogue of phosphatidic acid, and a water-soluble benzaldehyde reagent were covalently attached to bovine heart cytochrome c oxidase. After reconstitution into vesicles, the lipid-benzaldehyde probes selectively incorporated into the smaller polypeptides of the enzyme, while the remaining subunits (I-IV) exhibited little incorporation of label. The accessibility of amine groups labeled under the conditions used here was independent of the structural and charge differences between the benzaldehyde probes. This suggests that all three lipid probes react with polypeptides of the cytochrome c oxidase complex at general contact sites for membrane phospholipids. A water-soluble benzaldehyde reagent predominantly labeled subunits IV, Va, and Vb and polypeptides of VII-VIII. A comparison of these results facilitates a more refined view of the disposition of polypeptides of cytochrome c oxidase in respect to the lipid and aqueous phases.

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Cardiolipin is the membrane receptor for mitochondrial creatine phosphokinase.

Cited by 136 publications

References 33 publications

Membrane-Binding and Lipid Vesicle Cross-Linking Kinetics of the Mitochondrial Creatine Kinase Octamer

Membrane-Binding and Lipid Vesicle Cross-Linking Kinetics of the Mitochondrial Creatine Kinase Octamer

Reversible unfolding of cytochrome c upon interaction with cardiolipin bilayers. I. Evidence from deuterium NMR measurements

Labeling of bovine heart cytochrome c oxidase with analogs of phospholipids. Synthesis and reactivity of a new cardiolipin benzaldehyde probe

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