MOLECULAR IDENTITY DETERMINANTS OF A LIPID DROPLET SUBPOPULATION AT THE NUCLEUS VACUOLE JUNCTION

Lipid droplets (LDs), the lipid reservoirs of the cell, perform key functions in bioenergetic homeostasis and membrane biosynthesis. In recent years, it is becoming apparent that not all LDs are the same. Instead, different sub-populations of LDs exist within the cell that can be differentiated by their coating proteins. Little is known about the biogenesis and function of LD subpopulations. In this study we identified a specialized LD subpopulation equipped with a unique set of surface proteins that is localized in close proximity to the nucleus vacuole junction (NVJ). One protein that resides in this LD subpopulation is the phosphatidylinositol transfer protein Pdr16. We used high-throughput screening in yeast to identify factors required for correct localization of Pdr16. We discovered that Pdr16 fails to be targeted to LDs in the absence of Ldo45 (lipid droplet organization protein of 45 kDa) which is the product of a unique splicing event connecting two adjacent open reading frames (YMR147W and YMR148W). Overexpression of LDO45 as well as its encompassed gene LDO16 (YMR148W/OSW5) induces clustering of bulk cellular LDs at the NVJ and Ldo16 is required for physiological LD accumulation in proximity to the NVJ in response to nutrient depletion. Ldo16 and Ldo45 are linked to the known LD biogenesis factor seipin. We conclude that Ldo proteins determine LD identity both by mediating LD positioning in a unique cellular niche and by surface protein targeting.