Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49628
Title: Regulation of Autophagy by Lipid Species
Authors: TAN SHI HAO
Keywords: Autophagy, Lipids, PKC, SCD-1, MTOR
Issue Date: 16-Aug-2013
Source: TAN SHI HAO (2013-08-16). Regulation of Autophagy by Lipid Species. ScholarBank@NUS Repository.
Abstract: Macroautophagy (referred to as autophagy hereafter in this thesis) is an evolutionarily conserved and regulated catabolic process where cellular components (proteins, lipids and organelles) are sequestered in double membrane vesicles called autophagosomes which fuse with lysosomes for degradation by lysosomal enzymes. At present, the lipotoxic effects of free fatty acids (FFAs) have been well studied, while the role of FFAs in the regulation of autophagy is still controversial. In this study we show conclusively that treatment of cells with exogenous FFAs like PA but not OA induces autophagy via activation of PKC- signaling pathway. Furthermore, autophagy can also be induced by modulating endogenous FFAs levels through inhibition of SCD-1 in cells with hyperactivated MTORC1 signaling pathway. Data from this study support the notion that changes in the intracellular levels of lipid species play important roles in regulation of autophagy and such inducible autophagy generally serves as a pro-survival mechanism against the lipotoxicity. Therefore, results from our study suggest that manipulation of autophagy can be a potential therapeutic strategy against different types of diseases. Induction of autophagy upon lipotoxic stresses can be utilized to promote cell survival and limit the cytotoxic effects of excess intracellular lipid accumulation while on the other hand; inhibition of autophagy can also be utilized in tandem with SCD-1 inhibition to target cells with hyperactivated MTORC1 signaling pathway in diseases like cancer.
URI: http://scholarbank.nus.edu.sg/handle/10635/49628
Appears in Collections:Ph.D Theses (Open)

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