Structural Analogs of Palmitoyl Ceramide and their Functions in Membranes

Abstract

Cardiolipin (CL) is an unusual phospholipid found exclusively in the inner mitochondrial membrane (IMM) of eukaryotes. During regular cell function, CL tethers Cytochrome c (Cytc) to the IMM. During the initial stages of Apoptosis, Cytc oxidizes CL facilitating the release of Cytc into the cytoplasm where Cytc forms part of the apoptosome. With four monounsaturated acyl chains and a headgroup comprised of two phosphates, CL's unique structure gives rise to preferential localization on concave surfaces. CL constitutes 20% of the mitochondrial membrane and is often combined with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) to model the IMM in vitro. Unlike CL, DOPC shows no preferential localization to curved surfaces. Studies investigating Cytc-CL binding using CL/DOPC mixed lipid systems often assume unbiased lipid mixing throughout the model membrane systems. Using the recently synthesized fluorophore, 1,1,2,2,-tetrakis[4-(2-trimethylamminoioethoxy)phenyl]ethene (TTAPE-Me), CL concentration was evaluated on the inner and outer leaflets of 100 nm large unilamellar vesicles (LUV) at varying ratios of CL and DOPC.