Cardiolipin can be shifted from lamellar phase in low salt concentrations to hexagonal II phase in high salt. Acyl cardiolipin and monolysocardiolipin remain hexagonal II phase or lamellar respectively independent of salt concentration (Powell & Marsh, Biochemistry 24 (1985) 2902-2908). The effects of lamellar- favoring lipids like dioleoylphosphatidylcholine (DOPC) and the presence of the intrinsic membrane enzyme, cytochrome oxidase, on these phase changes will be evaluated using 31P-NMR, low angle X- ray diffration, and freeze-fracture electron microscopy in collaboration with D. Marsh, Max-Planck Institute for Biophysical Chemistry. The permeability of mixtures of DOPC and the above cardiolipins as large unilamellar vesicles to Na, K and 11- will then be measured under conditions in which the phase behavior is known and the effect of incorporating cytochrome oxidase on these permeabilities observed. The results will demonstrate the efficiency of sealing at the lipid protein-interface and the importance of the presence of lipids which form non-lamellar phases to these related membrane properties. In heart tissue lysolipids formed during myocardial infarct probably makes the inner mitochondrial membrane leaky, uncoupling electron transport and phosphorylation directly resulting in cell death. Demonstration of the molecular basis of cell death under these circumstances would ensble better intervention and treatment of patents with heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL038190-02
Application #
3354275
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Clemson University
Department
Type
Schools of Arts and Sciences
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
Powell, G L; Hui, S W (1996) Tetraoleoylpyrophosphatidic acid: a four acyl-chain lipid which forms a hexagonal II phase with high curvature. Biophys J 70:1402-6
Norris, F A; Powell, G L (1992) Characterization of CO2/carbonic acid mediated proton flux through phosphatidylcholine vesicles as model membranes. Biochim Biophys Acta 1111:17-26
Hildebrandt, P; Heimburg, T; Marsh, D et al. (1990) Conformational changes in cytochrome c and cytochrome oxidase upon complex formation: a resonance Raman study. Biochemistry 29:1661-8
Norris, F A; Powell, G L (1990) The apparent permeability coefficient for proton flux through phosphatidylcholine vesicles is dependent on the direction of flux. Biochim Biophys Acta 1030:165-71
Abramovitch, D A; Marsh, D; Powell, G L (1990) Activation of beef-heart cytochrome c oxidase by cardiolipin and analogues of cardiolipin. Biochim Biophys Acta 1020:34-42
Powell, G L; Knowles, P F; Marsh, D (1990) Incorporation of cytochrome oxidase into cardiolipin bilayers and induction of nonlamellar phases. Biochemistry 29:5127-32
Costello, P B; Powell, G L; Green, F A (1990) The structural requirements for anti-cardiolipin antibody binding in sera from patients with syphilis and SLE. Clin Immunol Immunopathol 56:393-400
Sankaram, M B; Powell, G L; Marsh, D (1989) Effect of acyl chain composition on salt-induced lamellar to inverted hexagonal phase transitions in cardiolipin. Biochim Biophys Acta 980:389-92
Fowler Jr, W T; Lambeth, J D; Powell, G L (1988) Photoreactive cardiolipin analogues. Chem Phys Lipids 47:261-71