THESIS
2021
1 online resource (viii, 47 pages) : color illustrations
Abstract
Lipid droplets (LDs) are the major cellular organelles for excess energy storage under the form of neutral lipid. LD fat reservoir provides energy and raw materials for cell growth and homeostasis. Excessive fat storage in LDs is central to the pathogenesis of prevalent metabolic diseases, such as obesity, fatty liver, and cardiovascular diseases. Proteomic studies have identified a large set of proteins that are LD residents. Furthermore, a small number of proteins are known to shuttle between the endoplasmic reticulum and LD. One of them, 1,2-diacylglycerol acyltransferase 2 (DGAT2) is one of the two DGAT enzymes that catalyse the final step of triglyceride (TG) synthesis. When cells are actively importing fatty acids, DGAT2 will go to LDs where it can catalyse TG synthesis for LD exp...[
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Lipid droplets (LDs) are the major cellular organelles for excess energy storage under the form of neutral lipid. LD fat reservoir provides energy and raw materials for cell growth and homeostasis. Excessive fat storage in LDs is central to the pathogenesis of prevalent metabolic diseases, such as obesity, fatty liver, and cardiovascular diseases. Proteomic studies have identified a large set of proteins that are LD residents. Furthermore, a small number of proteins are known to shuttle between the endoplasmic reticulum and LD. One of them, 1,2-diacylglycerol acyltransferase 2 (DGAT2) is one of the two DGAT enzymes that catalyse the final step of triglyceride (TG) synthesis. When cells are actively importing fatty acids, DGAT2 will go to LDs where it can catalyse TG synthesis for LD expansion. Previous studies have suggested that DGAT2 degradation may be dependent on the ER-associated degradation (ERAD) pathway. Using a candidate approach, we found that fasting-induced degradation of DGAT2 may be regulated by the Ancient Ubiquitous Protein 1 (AUP1), which functions in the ERAD pathway. Our initial data in C. elegans showed that DGAT2 was abnormally stable in starved AUP1 mutant worms. My goal is to further explore the spatial-temporal requirement of AUP1 in fasting-induced DGAT2 degradation in mammalian cells. In addition, I also conducted a phosphatase RNAi screen in C. elegans, which resulted in two candidates that appeared to modulate DGAT2 level.
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