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. 2020 Jan 1:3:1-13.
doi: 10.1177/2515256420910892. Epub 2020 Mar 19.

Lipid Droplet Contacts With Autophagosomes, Lysosomes, and Other Degradative Vesicles

Kristina Drizyte-Miller  1 , Micah B Schott  2 , Mark A McNiven  2
Affiliations

Lipid Droplet Contacts With Autophagosomes, Lysosomes, and Other Degradative Vesicles

Kristina Drizyte-Miller et al. Contact (Thousand Oaks). .

Abstract

Lipid droplets (LDs) are dynamic fat-storage organelles that interact readily with numerous cellular structures and organelles. A prominent LD contact site is with degradative vesicles such as autophagosomes, lysosomes, autolysosomes, and late endosomes. These contacts support lipid catabolism through the selective autophagy of LDs (i.e., lipophagy) or the recruitment of cytosolic lipases to the LD surface (i.e., lipolysis). However, LD-autophagosome contacts serve additional functions beyond lipid catabolism, including the supply of lipids for autophagosome biogenesis. In this review, we discuss the molecular mediators of LD contacts with autophagosomes and other degradative organelles as well as the diverse cellular functions of these contact sites in health and disease.

Keywords: autophagosome; autophagy; cell biology; endosome; lipid droplet; lysosome.

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Conflict of interest statement

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Diverse Functions of LD-Autophagosome Interactions. Traditionally, LD associations with autophagic membranes have been thought to result in LD breakdown via lipophagy. During this process, Rab7 and Rab10 assist in LD recognition and engulfment within autophagosomes, which fuse with lysosomes, LEs or MVBs containing lysosomal acid lipase. In addition to lipophagy, autophagosomes can also facilitate lipolysis by delivering ATGL and HSL to the LD surface via lipase interactions with LC3. Finally, neutral lipids stored within LDs can serve as a lipid source for autophagosome biogenesis, perhaps through the tethering and lipid transfer activity of Atg2a at the ER. LEs = late endosomes; MVBs = multivesicular bodies; ER = endoplasmic reticulum; LD = lipid droplet; ATGL = adipose triglyceride LD lipase. HSL = hormone sensitive lipase.
Figure 2.
Figure 2.
Proposed Model of LD Contacts With Degradative Organelles. Panel A: A cartoon showing proposed proteins involved in regulating LD associations with APs, lysosomes, MVBs and other degradative vesicles. Panel B: Comparison of images of a GFP-Rab10-positive LD from nutrient-starved Huh7 cells observed using wide-field epifluorescence (left) or super-resolution microscopy (middle and right). Panel C: Images from nutrient-starved Hep3B cells showing colocalization between LD-localized mCherry-Rab10 and endogenous LC3 (LD is shown in blue). Panel D: Low-magnification electron microscopy image of LD-AP or other degradative lysosomal membrane interactions in Huh7 cells that are expressing GFP-tagged active Rab10 (Q68L) form and have been starved in nutrient-depleted medium. Scale bars, 1 μm. Microscopy images (B-D) have been adapted from Li et al. (2016). LD = lipid droplet; AP = autophagosome.
See this image and copyright information in PMC

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