Function of prokaryotic and eukaryotic ABC proteins in lipid transport

ATP binding cassette (ABC) proteins of both eukaryotic and prokaryotic origins are implicated in the transport of lipids. In humans, members of the ABC protein families A, B, C, D and G are Mutated in a number of lipid transport and metabolisin disorders, such as Tangier disease, Stargardt syndrome, progressive familial intrahepatic cholestasis, pseudoxanthorna elasticurn, adren0leUkodystrophy or sitosterolernia. Studies employing transfection, overexpression, reconstitution, deletion and inhibition indicate the trailsbilayer transport of endogenous lipids and their analogs by some of these proteins, modulating lipid transbilayer asymmetry. Other proteins appear to be involved in the exposure of specific lipids oil the exoplasmic leaflet, allowing their uptake by acceptors and further transport to specific sites. Additionally lipid transport by ABC proteins is currently being studied in non-human eukaryotes, e.g. in sea urchin, trypanosornatides, arabidopsis and yeast, as well as in prokaryotes such as Escherichia coli and Lactococcus lactis. Here, we review current information about the (putative) role of both pro- and eukaryotic ABC proteins in the various phenomena associated with lipid transport. Besides providing a better understanding of phenomena like lipid metabolism, circulation, niultidrUg resistance, hormonal processes, fertilization, vision and signalling. studies oil pro- and eukaryotic ABC proteins might eventually enable us to put a name on some of the proteins mediating transbilayer lipid transport in various membranes of cells and organelles. It must be emphasized, however, that there are still many uncertainties concerning the functions and mechanisms of ABC proteins interacting with lipids. In particular, further purification and reconstitution experiments with all unambiguous role of ATP hydrolysis are needed to demonstrate a clear involvement of ABC proteins in lipid transbilayer asymmetry. (c) 2004 Elsevier B.V. All rights reserved.