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Identifier 000419980
Title Dissecting the role of lipid metabolism and the nature of autophagosomal cargo in Central Nervous System
Alternative Title Διερεύνηση του μεταβολισμού των λιπιδίων και της φύσης του αυτοφαγικού φορτίου στο Κεντρικό Νευρικό Σύστημα
Author Γούνα, Γαρυφαλλιά
Thesis advisor Νικολετοπούλου, Βασιλική
Reviewer Ζαγανάς, Ιωάννης
Καρδάσης, Δημήτριος
Abstract Lipids represent key macromolecules of vital importance for the maintenance of brain homeostasis, from a structural and a signaling point of view. Lipid droplets (LDs), the storage organelles of the lipids, are selectively degraded by macroautophagy in several tissues, a process known as lipophagy. There is a growing body of literature, suggesting that lipophagy provides the platform for utilization of lipids not only as energy resources, but also as signaling molecules. However, the role of lipophagy in the central nervous system (CNS) is poorly understood. Here, we try to address if lipophagy regulates the mobilization of lipids in neurons, by monitoring two LD protein markers, RAB18 and PLIN2. We report that, RAB18 appears to be a positive modulator of autophagy, whereas PLIN2 protein acts as an autophagic substrate. The absence of colocalization of RAB18 and PLIN2 suggest the existence of two distinct LD populations with potential diverse functions. This hypothesis is further supported by the different localization of these two markers on the autophagosome. Interestingly, there is strong evidence of RAB18 localization in the ER and nuclei compartments in CNS, while mounting evidence support a positive association of RAB18 and autophagosomal biogenesis. In addition, synaptic 3 and cytoskeletal proteins were primarily identified as autophagic cargo from the forebrain of young and mature animals, by conducting Tandem Mass Spectrometry proteomic analyses. Thus, the association of autophagy to synaptic and cytoskeletal functions is highlighted. Overall, our findings emphasize the presence of distinct LD populations in neurons, which are regulated via the lipophagy mechanism, and may maintain synaptic homeostasis. To our knowledge, this is the first study indicating that RAB18 and PLIN2 associate with lipophagy in CNS. Last, this study draws the initial route of characterizing the autophagic cargo of forebrain amongst young and mature animals, providing important evidence for autophagy’s role across maturation in the brain.
Language English
Subject Autophagosome
Central nervous system
Lipid droplet
Σταγονίδιο λιπιδίου
Issue date 2018-12-05
Collection   Faculty/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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