Chapter Three - Lipid Droplets as Organelles
Introduction
Lipid droplets (LDs) are cellular structures that store fat in the form of neutral lipids. Nearly all eukaryotic cells can make LDs, which are composed of a core of triglycerides and sterol esters. Because the core of the LD is hydrophobic, LDs are surrounded by a phospholipid monolayer, with the hydrophobic phospholipid tails oriented toward the neutral lipid core (Thiam et al., 2013). This is different from most other cellular organelles, which have aqueous lumens and are surrounded by phospholipid bilayers. Despite their unique structure, it has become clear that LDs are bona fide organelles. Like other organelles, LDs have a characteristic complement of proteins and lipids. Over 100 LD-associated proteins have been identified (Bersuker and Olzmann, 2017; Krahmer et al., 2013). These include proteins involved in lipid synthesis and metabolism, as well as proteins involved in membrane trafficking and organelle transport (Bersuker and Olzmann, 2017). LDs undergo a life cycle that includes biogenesis, maturation, and turnover (Hashemi and Goodman, 2015; Fig. 1). Under certain conditions LDs can undergo fusion and fission (Thiam et al., 2013), and LDs also make close contacts with many other organelles, presumably to exchange lipids (Barbosa et al., 2015; Schuldiner and Bohnert, 2017; Fig. 1). In this review, I will discuss these aspects of the LD life cycle, highlighting similarities and differences with other cellular organelles, as well as open questions in this exciting field.
Section snippets
Mechanism of LD Biogenesis
LDs can form in response to various stimuli, including excess lipids or a variety of stresses (Gubern et al., 2009). There is evidence that LD biogenesis occurs in the endoplasmic reticulum (ER), which is the site of many lipid synthesis enzymes (Pol et al., 2014; Walther et al., 2017). In the prevailing models of LD biogenesis, neutral lipid synthesis occurs within the ER membrane, at ER microdomains enriched in acyl-CoA synthetase 3, an enzyme involved in the first step of triacylglycerol
LD Maturation and Heterogeneity
LDs show remarkable heterogeneity in protein and lipid composition. Some of this heterogeneity may reflect subpopulations of LDs with different functions. For example, when cells are loaded with excess fatty acids and sterols, they form distinct populations of LDs enriched either in sterol esters or in triglycerides (Hsieh et al., 2012). However, it has also been proposed that LDs undergo a maturation process over time. Organelle maturation and heterogeneity is an emerging theme in cell biology
LD Fusion
LDs can undergo fusion via two separate mechanisms. During the differentiation of adipocytes, many small LDs combine to form one large LD (Gao et al., 2017). The resulting LD occupies much of the volume of the adipocyte and allows for efficient lipid storage by minimizing the surface area to volume ratio of the hydrophobic neutral lipids. This type of fusion occurs by Ostwald ripening, in which lipids are transferred from the smaller to larger LD by diffusion (Thiam et al., 2013). The close
Interactions Between LDs and Other Organelles
LDs can make close contacts with a variety of other organelles (Barbosa et al., 2015; Schuldiner and Bohnert, 2017). Membrane contact sites are increasingly understood to be key sites of communication and metabolite exchange between organelles. A recent study using multispectral imaging to simultaneously image six organelles found that LDs frequently moved within 1 pixel (~ 100 nm) of every other labeled organelle, namely, the ER, mitochondria, peroxisomes, lysosomes, and the Golgi (Valm et al.,
LD Turnover
Like other organelles, LDs have a life cycle that involves LD turnover and breakdown. As the organelle responsible for lipid storage, LDs must be able to respond rapidly to changes in the energetic needs of the cell. The best-characterized mechanism for the release of fatty acids from triglycerides within LDs is via cytoplasmic lipases, called lipolysis (Zechner et al., 2017). However, pieces of LDs and even whole LDs can also be degraded via autophagy, in a process termed lipophagy (Singh et
Conclusions and Future Perspectives
LDs are bona fide organelles that undergo a life cycle including biogenesis, maturation, and turnover. They may also undergo fusion and fission, and they interact with and exchange materials with other organelles. Many aspects of the LD life cycle remain incompletely understood. LDs have unique biophysical properties, due to their hydrophobic core and phospholipid monolayer membrane (Thiam and Foret, 2016; Thiam et al., 2013). Therefore, certain aspects of the LD life cycle are unique to LDs.
Acknowledgments
This work was supported by the University of North Carolina at Chapel Hill, and by the National Institute on Aging of the National Institutes of Health, under award number K99AG052570.
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