PHYSIOLOGICAL FUNCTION OF LIPID DROPLETS AND REGULATION OF INTRACELLULAR LIPID TRAFFICKING

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The dynamic properties of lipid droplets have become more apparent by our recent studies. During the period supported by the current grant, we obtained the following results.1. Rabl8 was found to localize to lipid droplets specifically. When Rab18 was overexpressed, ADRP decreased, and close association of lipid droplets and the endoplasmic reticulum became prominent. The same structure also increased upon knockdown of ADRP or by brefeldin A treatment. These results suggested that Rab18 induces the lipid droplet-associated membrane structure (LAM) through dislocation of ADRP.2. In hepatocyte-derived cell lines (Huh7, HepG2), ApoB was found to form a crescent-shaped structure around lipid droplets (ApoB-crescent). The ApoB-crescent increased drastically when proteasome or autophagy was prohibited. Proteasomal subunits were concentrated around lipid droplets, and ApoB recovered in the lipid droplet fraction was highly ubiquitinated. The result suggested that lipid droplets are a platform for ApoB to be processed by proteasome and autophagy.3. TIP47, a member of PAT family proteins, was recruited to lipid droplets when cells were added with fatty acids. The localization of TIP47 to lipid droplets required its N-terminal portion. On the other hand, disruption of the C-terminal portion, which was speculated to form a hydrophobic cleft, induced constitutive localization to lipid droplets.These results further revealed that lipid droplets have a variety of functions in relation to intracellular lipid homeostasis.