FUNCTION OF CARDIOLIPIN PHASE POLYMORPHISM

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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.