Lipid Trafficking and Disease group

LINES OF RESEARCH

Understanding the biogenesis and consumption of Lipid Droplets: decoding the metabolic syndrome?

Summary

Lipid droplets are ubiquitous organelles that collect, store and supply lipids in all mammalian cells and also in bacteria, yeast, fungi and plants. In a changing environment, mechanisms for efficient storage and timely delivery of lipids likely represented an important adaptive response for individual cells. Excessive or reduced accumulation of LDs is clearly undesirable, and is a cellular hallmark of prevalent human diseases such as hepatic steatosis and steatohepatitis, obesity, metabolic syndrome, diabetes, myopathies, lipodystrophies and arteriosclerosis but also have an important economical impact by production of food and biofuels.

Description

Lipid droplets (LDs) are ubiquitous organelles that collect, store and supply lipids in all mammalian cells and also in bacteria, yeast, fungi and plants (Pol et al., J Cell Biol 2014). In a changing environment, mechanisms for efficient storage and timely delivery of lipids likely represented an important adaptive response for individual cells. Excessive or reduced accumulation of LDs is clearly undesirable, and is a cellular hallmark of prevalent human diseases such as hepatic steatosis and steatohepatitis, obesity, metabolic syndrome, diabetes, myopathies, lipodystrophies and arteriosclerosis. However, although the balance between supply and consumption determines LD levels, LD accumulation is remarkably heterogeneous even between otherwise identical cells (Herms et al., Curr Biol 2013). During the last decade the LD has finally been understood as a complex and dynamic organelle, with a central role in the regulation of lipid fluxes existing between cellular compartments and between the cell and the extracellular environment. However, relatively little is known about the most basic biological features of the LD.

 

Since 2001 our group has been interested in the cell biology of the LD. We described and characterized CAV on LDs (Pol et al., J Cell Biol 2001; Pol et al., Mol Biol Cell 2004; Pol et al., Mol Biol Cell 2005). We have characterized the proteome of hepatic LDs and identified ALDI (Associated with LDs 1) as a major methyl-transferase on hepatic LDs (Turró et al., Traffic 2006).

 

Recently, we have characterized the interaction between LDs and mitochondria on a special subset of microtubules (MT). This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated-MTs, and activates mitochondria. (Herms et al., Nat Comm 2015).

 

We have also described a two-part separable localization signal that efficiently accumulates proteins on LDs (Ingelmo-Torres et al., Traffic 2009). The model peptides generated with this information are sufficient for sorting otherwise cytosolic proteins within the ER into LDs. The structural simplicity of these model proteins was especially convenient to characterize the molecular requirements necessary for sorting proteins to LDs. Now, we are using similar model proteins to study the biogenesis of LDs on specific microdomains of the ER (Kassan et al., J Cell Biol 2013).

the biogenesis of LDs visualized with fluorescent peptides (Kassan et al in J Cell Biol 2013)
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