Significance of cell lipid droplets
LDs have a lipophilic core of neutral lipids, such as tricylglycerides (TAGs), sheltered in a phospholipids monolayer containing different proteins. Previous research showed that coat protein complex I (COPI) is required for LD targeting of proteins. In other words, a direct interaction between COPI and LD may be taking place. An EU-funded project, BFLDS (Direct imaging of budding and fusion of lipid droplets mediated by proteins in emulsion droplets based on microfluidics - Dynamics of proteins interactions, assembly and metabolism energy),has researched the role of COPI in LD behaviour through direct imaging of budding and fusion processes. The project also explored the accessibility regulation of LDs to enzymes involved in energy storage and release. The results revealed that budding is initiated on fully packed phospholipids on the mother LD, favouring hydrophobic TAG molecules exposure to the aqueous environment, and thereby increasing the surface tension. To fuel budding from membranes, especially monolayers, COPI provides energy of up to 2 000 kBT. Simple remodelling of membrane properties is a way of regulating COPI budding. In vivo studies showed that COPI proteins localise to LDs and are necessary for targeting specific TAG-synthesising enzymes to LDs. Cells lacking COPI had increased amounts of phospholipids on LDs, with corresponding decreased LD surface tension, and inability to form bridges to the endoplasmic reticulum protein transport. The researchers also demonstrated that different proteins compete in binding to LD. Where a protein has both hydrophilic and hydrophobic groups, is amphipathic, they are out-competed for LD binding by other strongly binding proteins that have a hairpin binding motif, for example. During energy remobilisation where LDs shrink, compression of the LD surface expels the amphipathic proteins. BFLDS has revealed a new role for COPI proteins in LDs, regulating their ability to react with neighbouring membranes through surface tension changes. Regulation of LDs is crucial for human health and their malfunction can have dire consequences such as the development of cardiovascular diseases and type II diabetes. Distinct from their role in cell energy regulation, they can also serve as hosts for virus proliferation such as in Hepatitis C and Dengue.
Keywords
Lipid droplets, diseases, phospholipids, coat protein complex I, BFLDS, budding and fusion
