Lipid trafficking sans vesicles: where, why, how?

Abstract

Eukaryotic cells possess a remarkable diversity of lipids, which distribute among cellular membranes by well-characterized vesicle trafficking pathways. However, transport of lipids by alternate, or "nonvesicular," routes is also critical for lipid synthesis, metabolism, and proper membrane partitioning. In the past few years, considerable progress has been made in characterizing the mechanisms of nonvesicular lipid transport and how it may go awry in particular diseases, but many fundamental questions remain for this rising field.

Figure 1. Possible mechanisms of nonvesicular lipid exchange between membranes

Lipids can spontaneously exchange between two membranes without the assistance of proteins; (A) monomers can diffuse through the aqueous phase or (B) during the collision of two membrane collision after the lipid is “activated.” (C) Lipid transport proteins (LTPs) can also exchange lipids between membranes and organelles. LTPs have a lipid-binding domain (blue) and, many times, targeting domains (purple) that may direct lipid transfer to particular membranes by binding to lipids or proteins. Lipids may exchange at membrane contact sites where two membranes come together in close proximity. Protein complexes may facilitate this process (D) by forming a tunnel that allows lipids diffuse between the membranes, (E) by promoting lipid desorption from one membrane, (F) by activating lipids prior to membrane collision, or (G) by promoting transient membrane hemifusion.