Chapter 14 - Inter- and intra-membrane lipid transport

Abstract

Most of the lipids required for the assembly and function of eukaryotic cell membranes are synthesised in the endoplasmic reticulum and transported from there to their appropriate destinations. Lipids are asymmetrically distributed in cells, both between organelles and the two leaflets of a membrane. The asymmetry arises through (i) synthesis of lipids in specific compartments or membrane leaflets followed by their transport to appropriate targets and (ii) local synthesis or enzymatic modification of lipids at the sites where they are enriched. Inter-organelle lipid transport takes place via both vesicular and non-vesicular mechanisms. The latter is currently thought to be predominantly mediated by lipid transfer proteins that bind within a hydrophobic cavity or groove a lipid substrate from the donor membrane and deliver it to the acceptor organelle. Here, an important concept is that of membrane contact sites (MCSs), at which close proximity of two membranes greatly facilitates lipid transfer. The trans-bilayer movement of lipids is mediated by integral membrane proteins termed flippases, floppases and scramblases. In this chapter we provide an overview of the mechanisms and physiologic significance of lipid transfer between organelle membranes and bilayer leaflets, and the roles of lipids in determining the functional identity of organelles.