Jennifer Miller:
Title: TBA
Abstract: TBA
Carlson Lab
Anuradha Iyer:
Title: Investigating the role FIT2 plays in lumenal lipid droplet formation and subsequent secretion of very-low density lipoprotein (VLDL)
Abstract:
In humans, the liver secretes very low-density lipoprotein (VLDL) into the bloodstream. VLDLs are comprised of three main components, apolipoprotein B (ApoB), cholesteryl esters, and triglycerides. VLDLs are acted upon by lipoprotein lipase to provide fatty acids to endothelial cells and thus form intermediate density lipoprotein (IDL), also known as VLDL remnant. IDL is further hydrolyzed by hepatic lipase to give low-density lipoprotein (LDL), which is the main circulating cholesterol carrier in the bloodstream. Ultimately, LDL is taken up by tissues and the liver itself by means of LDL receptors, so cholesterol can be delivered for use or storage. However, a high fat diet, oxidative stress, reduced endothelial cell integrity, and several poorly defined genetic mutations lead to atherosclerosis and subsequent coronary artery disease (CAD). Under these conditions, cholesteryl esters and VLDL remnants are deposited on the wall of the arteries, thus forming plaques, and reducing blood flow. ApoB, which forms a major component of VLDL, is also required for VLDL and LDL biosynthesis and therefore determines circulating cholesterol levels. Unlike transcriptional control that mediates most metabolic processes, the secretion of hepatic ApoB and VLDL/LDL is mediated by metabolically controlled degradation. In lipid-deficient states, ApoB is degraded by the proteasome as it is being synthesized at the endoplasmic reticulum (ER). In lipid-rich states, ApoB is stable and facilitates efficient lipid loading and subsequent VLDL production. Recent findings indicate that lipid loading occurs in two steps, with the second step mediated by an ill-defined ER membrane protein, fat storage-inducing transmembrane protein 2 (FIT2). I aim to understand how FIT2 aids in lipid loading prior to VLDL secretion, whether loss of FIT2 affects ER homeostasis and if FIT2 is an endoplasmic reticulum associated degradation substrate (ERAD).
Brodsky Lab
Friday, September 8th, 2023
12:00PM
Langley A219B