Proteomic insights into an expanded cellular role for cytoplasmic lipid droplets

Abstract

Cytoplasmic lipid droplets (CLDs) are cellular structures composed of a neutral lipid core surrounded by a phospholipid monolayer of amphipathic lipids and a variety of proteins. CLDs have classically been regarded as cellular energy storage structures. However, recent proteomic studies reveal that, although many of the proteins found to associate with CLDs are connected to lipid metabolism, storage, and homeostasis, there are also proteins with no obvious connection to the classical function and typically associated with other cellular compartments. Such proteins are termed refugee proteins, and their presence suggests that CLDs may serve an expanded role as a dynamic protein storage site, providing a novel mechanism for the regulation of protein function and transport.

Fig. 1.

Proposed cellular functions of CLDs. CLD formation begins in the smooth endoplasmic reticulum. Lipid esters are deposited within the phospholipid bilayer and microlipid droplets form, bud, and are released into the cytoplasm (7) associated with PAT proteins (pink circles). Three potential CLD functional roles are: A, Sequestration: proteins may be reversibly inactivated by CLD sequestration of one binding partner. Active state and sequestered states are shown. B, Chaperone: aggregation prone proteins without binding partners are sequestered until appropriate binding partners are available. C, Protein transport: CLDs move along cytoskeletal components carrying sequestered proteins from one cellular location to another.