FIGURE 1.

nLD biogenesis in mammalian cells. Two mechanisms have been identified for nLD formation. Mechanism 1: Much like cLD biogenesis, nLD biogenesis in U2OS cells, S. cerevisiae, and C. elegans involves in situ TAG synthesis at the INM facilitated by lipid biosynthetic enzymes. nLD biogenesis is seipin-dependent in S. cerevisiae, whereas the process is seipin-independent in U2OS cells. Mechanism 2: In specialized lipoprotein-exporting mammalian cells like hepatocytes and intestinal epithelial cells, ApoB-free eLDs form in an MTP-dependent manner and subsequently migrate through the lumen of the ER into the lumen of the NE. Next, eLDs enter into type-I NR invaginations of the INM that extend into the nucleoplasm. PML-II localizes to INM at lamin-deficient regions, possibly facilitating translocation of the LD through ruptures of the INM into the nucleoplasm. In mammalian cells more generally, lipid biosynthetic enzymes DGAT2, Lipin-1 and CCTα, LD coat protein perilipin-3, and PML are all present at the surface of nLDs. The binding of lipid biosynthetic enzymes and the formation of LAPS are two commonalities of nLDs irrespective of their biogenesis in mammalian cells, suggesting a possible conserved function for these structures.