Final Report Summary - DROPFAT (Biogenesis of lipid droplets and lipid homeostasis)
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. However, despite their ubiquitous presence and importance, how LDs form and are regulated is poorly understood.
In this project we investigated the mechanisms by which LD are formed and regulated. We focused particularly on the role of the endoplasmic reticulum (ER), other cellular compartment, which produces most of LD components and is believed to play a key role in LD formation. Our initial studies led to the identification of the components stabilizing the connections between these two compartments and that play an essential function in proper LD formation and fat storage. We further uncovered a process by which LD dynamics is regulated in response to nutrient availability, thus linking cell metabolism with energy storage. Our studies also brought insight on how specific ER sites are organized and become competent for LD formation. Overall our work contributed to a better understanding of the processes of energy storage into LDs and ultimately, may contribute to a better understanding of human pathologies such as obesity and lipodystrophies.
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. However, despite their ubiquitous presence and importance, how LDs form and are regulated is poorly understood.
In this project we investigated the mechanisms by which LD are formed and regulated. We focused particularly on the role of the endoplasmic reticulum (ER), other cellular compartment, which produces most of LD components and is believed to play a key role in LD formation. Our initial studies led to the identification of the components stabilizing the connections between these two compartments and that play an essential function in proper LD formation and fat storage. We further uncovered a process by which LD dynamics is regulated in response to nutrient availability, thus linking cell metabolism with energy storage. Our studies also brought insight on how specific ER sites are organized and become competent for LD formation. Overall our work contributed to a better understanding of the processes of energy storage into LDs and ultimately, may contribute to a better understanding of human pathologies such as obesity and lipodystrophies.