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THE ROLE OF A DEFECT IN THE CDP-ETHANOLAMINE PATHWAY IN AUTOPHAGY

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Title: THE ROLE OF A DEFECT IN THE CDP-ETHANOLAMINE PATHWAY IN AUTOPHAGY
Author: Pereira, Leanne
Department: Department of Human Health and Nutritional Sciences
Program: Human Health and Nutritional Sciences
Advisor: Bakovic, Marica
Abstract: Autophagy is the process that degrades cytosolic constituents into products that can be recycled for use in energy generation and other processes. The endoplasmic reticulum is responsible for the bulk synthesis of the phospholipid phosphatidylethanolamine (PE) via the CDP-ethanolamine pathway. The aim of the present study was to determine the role of PE synthesis and the CDP-ethanolamine pathway in autophagy. This objective was examined through the use of two novel models deficient in Pcyt2, a gene that encodes the rate-limiting enzyme CTP-ethanolamine cytidyltransferase (ET) in the CDP-ethanolamine pathway. PCYT2 knockdown in human fibroblast cells did not respond normally to starvation conditions that activate autophagy. Similarly, Pcyt2 knockout in mice showed differences in autophagy induction in/between muscle, liver, and adipose tissue based on metabolic state (fasting/feeding). Pcyt2 knockout mice display evidence of metabolic syndrome at an older age and experiments with these mice determined that there was an effect of age (healthy young mice versus obese older mice) on autophagy induction. It was concluded based on in vitro and in vivo studies that autophagy induction is affected by impairment to the CDP-ethanolamine pathway and subsequent PE synthesis.
URI: http://hdl.handle.net/10214/4845
Date: 2012-12


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