Dr. William Prinz

Seminar Details

Host: Dr. Xuewu Sui

Time: 4:00pm-5:00pm

Location: BICH 108

Seminar Abstract

Over the last 15 years the field of ‘membrane contact site’ research into direct communication between organelles has taken off. An ever-growing list of functions have been assigned to these sites. My lab focuses on the mechanism and functions of non-vesicular lipid exchange between membranes at contact sites. It is facilitated by lipid transport proteins (LTPs). Until recently, it was thought that LTPs functioned as shuttles that move one lipid at a time between membranes. We now know that some LTPs are lipid conduits that interact with two membranes simultaneously and allow lipids to flow between them. One family, called bridge-like LTPs (BLTPs), are thought to facilitate high volume lipid transport. We are investigating the mechanism and function of BLTPs. One, BLTP2, is conserved across species and is highly expressed in many aggressive breast cancers, though its function was unknown. We found that BLTP2 regulates plasma membrane (PM) fluidity by increasing phosphatidylethanolamine (PE) levels in the PM. BLTP2 localizes to endoplasmic reticulum (ER)-PM contact sites, and transports PE in vivo, suggesting it drives PE movement from ER to PM. This is a new function for LTPs. BLTP2 may sustain metastatic growth of a triple negative breast cancer cell line into ways. One is by helping to maintain PM fluidity. The second is by suppressing ferroptosis, a cell death pathway triggered by oxidized lipids, particularly oxidized PE species. We are investigating how BLTP2 and perhaps other LTPs can suppress ferroptosis, perhaps by affecting PE metabolism or intracellular distribution.