Mechanisms of lipid droplet biogenesis at the endoplasmic reticulum

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Organisms and cells face a myriad of environmental changes with periods of nutrient surplus and shortage. It is therefore not surprising that in all kingdoms of life, cells have evolved the means to store energy and thereby minimize the effects of environmental fluctuations. While the capability for energy storage has obvious advantages, deregulated energy accumulation can also be detrimental. Indeed, excessive energy storage is the hallmark of some of the most common diseases in the Western world such as obesity, atherosclerosis or diabetes. In most cells energy is stored as fat in a dedicated cellular compartment called lipid droplet (LD). LDs are found in virtually every eukaryotic cell and play a central role in cellular lipid and energy metabolism. Despite their ubiquitous presence and importance, the processes governing the formation of LDs are mysterious. This proposal is aimed at closing the gap in understanding LDs. It is well accepted that another cellular compartment, the endoplasmic reticulum (ER) plays a key role in LD formation. Many of the ingredients present in LDs come from the ER and in cells, ER and LD are often seen in close proximity. Our previous work and preliminary results identified components stabilizing the connections between these two compartments and that play an essential function in proper LD formation and fat storage. We expect that our work will offer in-depth information on the process of LD formation. Ultimately the findings might contribute to a better understanding of human pathologies such as obesity and lipodystrophies.