The CYTOLD and ERTOLD pathways for lipid droplet–protein targeting

Abstract

Lipid droplets (LDs) are the main organelles for lipid storage, and their surfaces contain unique proteins with diverse functions, including those that facilitate the deposition and mobilization of LD lipids. Among organelles, LDs have an unusual structure with an organic, hydrophobic oil phase covered by a phospholipid monolayer. The unique properties of LD monolayer surfaces require proteins to localize to LDs by distinct mechanisms. Here we review the two pathways known to mediate direct LD protein localization: the CYTOLD pathway mediates protein targeting from the cytosol to LDs, and the ERTOLD pathway functions in protein targeting from the endoplasmic reticulum to LDs. We describe the emerging principles for each targeting pathway in animal cells and highlight open questions in the field.