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Review
. 2020 Oct 6:36:115-139.
doi: 10.1146/annurev-cellbio-031320-101827.

Protein Quality Control and Lipid Droplet Metabolism

Melissa A Roberts  1 , James A Olzmann  1   2
Affiliations
Review

Protein Quality Control and Lipid Droplet Metabolism

Melissa A Roberts et al. Annu Rev Cell Dev Biol. .

Abstract

Lipid droplets (LDs) are endoplasmic reticulum-derived organelles that consist of a core of neutral lipids encircled by a phospholipid monolayer decorated with proteins. As hubs of cellular lipid and energy metabolism, LDs are inherently involved in the etiology of prevalent metabolic diseases such as obesity and nonalcoholic fatty liver disease. The functions of LDs are regulated by a unique set of associated proteins, the LD proteome, which includes integral membrane and peripheral proteins. These proteins control key activities of LDs such as triacylglycerol synthesis and breakdown, nutrient sensing and signal integration, and interactions with other organelles. Here we review the mechanisms that regulate the composition of the LD proteome, such as pathways that mediate selective and bulk LD protein degradation and potential connections between LDs and cellular protein quality control.

Keywords: chaperone-mediated autophagy; endoplasmic reticulum; lipid droplet; lipophagy; metabolism; proteasome; protein targeting; triacylglycerol; ubiquitin.

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Figures

Figure 1
Figure 1
LD protein targeting. Class I LD proteins are inserted into the ER and are trafficked from the ER to nascent LDs. Class II LD proteins are inserted into LDs directly from the cytosol. These proteins include both amphipathic helix-containing proteins that recognize phospholipid packing defects in the LD monolayer and proteins that are modified by conjugated fatty acids. Abbreviations: ER, endoplasmic reticulum; LD, lipid droplet.
Figure 2
Figure 2
Mechanisms of LD protein degradation. LD proteins are present in multiple cellular compartments and have the potential to be degraded by ubiquitin-dependent pathways in the ER, cytosol, and LDs. Abbreviations: ERAD, endoplasmic reticulum–associated degradation; LD, lipid droplet; Ub, ubiquitin.
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