Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Cell Biology
First Advisor
Reinisch, Karin
Abstract
Eukaryotic cells compartmentalize their cellular processes in organelles. Lipid droplets (LDs) are key organelles in energy and membrane lipid homeostasis. It has become evident that LDs form membrane contact sites with other organelles throughout their lifetime, from biogenesis to degradation. Lipid transfer proteins (LTPs) localize to LDs, often at sites of LD-organelle contacts. Several known and newly identified LTPs impact LDs biogenesis and degradation, suggesting a role of protein mediated lipid transport in modulating LDs dynamics. The mechanisms of how lipid transport precisely participates in these functions is largely unclear. I characterized the protein spartin, mutations of which leads to neurological disease Troyer syndrome. Spartin localizes to LDs and participates in lipophagy to degrade LDs by tethering LDs close to autophagosome. We hypothesized that spartin might possess lipid transfer activity, like other protein tethers at membrane contact sites. Using biochemical and structural approaches, I discovered that spartin copurifies with phospholipids and neutral lipids from cells and transfers phospholipids in vitro via a so-called senescence domain. A senescence domain truncation impairs lipid transfer in vitro and also impairs LD turnover in cells while not affecting spartin’s association with either LDs or autophagosomes, supporting that spartin's lipid transfer ability is physiologically relevant. In summary, my data indicates a novel function of protein mediated lipid transfer in LD degradation, including by lipophagy.
Recommended Citation
Wan, Neng, "Role of Lipid Transfer Proteins in Lipid Droplet Dynamics" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1294.
https://elischolar.library.yale.edu/gsas_dissertations/1294
