The why, when and how of lipid droplet diversity

Abstract

Lipid droplets are the universal cellular organelles for the transient or long-term storage of lipids. The number, size and composition of lipid droplets vary greatly within cells in a homogenous population as well as in different cell types. The variability of intracellular lipidstorage organelles reflects the diversification of lipid droplet composition and function. Lipid droplet diversification results, for example, in two cellular lipid droplet populations that are prone to diminish and grow, respectively. The aberrant accumulation or depletion of lipids are hallmarks or causes of various human pathologies. Thus, a better understanding of the origins of lipid droplet diversification is not only a fascinating cell biology question but also potentially serves to improve comprehension of pathologies that entail the accumulation of lipids. This Commentary covers the lipid droplet life cycle and highlights the early steps during lipid droplet biogenesis, which we propose to be the potential driving forces of lipid droplet diversification.

ER Membrane Phospholipids and Surface Tension Control Cellular Lipid Droplet Formation

“…Such segregation could occur between the smooth and rough ER, nuclear and peripheral ER, and ER tubules and sheets (Lagace and Ridgway, 2013). These differences could allow the formation of distinct pools of LDs containing different lipids and proteins and having different sizes (Thiam and Beller, 2017). This could explain the occurrence in various cell types of separated sterol ester and triglyceride LDs, distinctly marked by different perilipin proteins (Hsieh et al, 2012;Meyers et al, 2016), or the existence of metabolically distinct diacylglycerol transferase 1-and 2-LDs, which have different sizes (Wilfling et al, 2013).…”

“…Variation of LD size is often observed between cell lines or types, or is due to the dysfunction of some proteins (Thiam and Beller, 2017). The origin of such variability remains very unclear except for very specific cases where LDs split, fuse, or grow (Gong et al, 2011;Long et al, 2012;Tan et al, 2014;Wilfling et al, 2013;Yang et al, 2012).…”

“…Despite their multiple functions, how LDs form is poorly understood (Pol et al, 2014;Thiam and Beller, 2017;Wilfling et al, 2014a). LD biogenesis starts in the endoplasmic reticulum (ER) wherein a cascade of enzymatic reactions mediates the synthesis of neutral lipids that are encapsulated within the ER intermonolayer space.…”

Establishing the lipid droplet proteome: Mechanisms of lipid droplet protein targeting and degradation

“…Efforts to define the LD proteome are also complicated by the heterogeneity of LDs, including differences in LD size, function, organelle association, and lipid composition [50]. This heterogeneity in LDs is lost when LDs are purified in bulk for proteomics analysis.…”

Lipid droplet functions beyond energy storage

“…These aspects of LDs have been reviewed extensively ( e.g. , [1-7, 11-21]); see also the reviews in this issue by Olzmann, Mashek, Zechner and Kratky, and Yen and Reue. Yet the importance of LDs is not restricted to energy storage.…”