Elucidating the Role of Yeast Lipin (PAH1) in Lipid Droplet Biogenesis
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Lipid droplets are unique organelles important for a host of cellular functions including the storage of neutral lipids, but factors that regulate the biogenesis and maintenance of these organelles remain relatively unknown. The primary focus of this dissertation will be to understand the role of the phosphatidic acid hydrolase (Pah1p) in the biogenesis of lipid droplets in Saccharomyces cerevisiae. Pah1p is an enzyme that converts phosphatidic acid to diacylglycerol, and its absence or elimination of its catalytic activity results in the accumulation of neutral lipids within membranes of the endoplasmic reticulum. Furthermore, lipid droplet formation is facilitated by diacylglycerol through a mechanism that appears to be independent of diacylglycrol’s role as a substrate for triglyceride biosynthesis. Finally, lipid droplets originated from regions of the endoplasmic reticulum where the Pah1p activators were located. The second part of this dissertation will focus on the lipodystrophy related protein Fld1p and its association with lipid droplets. Droplets always associate with Fld1p, and in the absence of lipid droplets, Fld1p is localized as patches distributed throughout the endoplasmic reticulum. In addition, induced lipid droplets originate from these Fld1 patches. I conclude from this work that diacylglycerol facilitates lipid droplet formation and that Fld1p is somehow involved in the biogenesis or maintenance of these organelles.