Medical research seminar: Scrambling in Lipid Transport and Tissue Homeostasis



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Prof Xiao-Wei Chen
Peking University

About the Talk: How amphipathic phospholipids are shuttled between the membrane bilayer remains an essential but elusive process, particularly at the endoplasmic reticulum (ER). One prominent phospholipid shuttling process concerns the biogenesis of APOB-containing lipoproteins within the ER lumen, which may require bulk trans-bilayer movement of phospholipids from the cytoplasmic leaflet of the ER bilayer. We have previously reported that a receptor-mediated export program, operated by the cargo receptor SURF4 and the small GTPase SAR1B, which selectively escorts the lipoproteins into the circulation. We further showed that TMEM41B, present in the lipoprotein export machinery, encodes a previously-conceptualized ER lipid scramblase mediating trans-bilayer shuttle of bulk phospholipids. Loss of hepatic TMEM41B eliminates plasma lipids, due to complete absence of mature lipoproteins within the ER, but paradoxically also activates lipid production. Mechanistically, scramblase deficiency triggers unique ER morphological changes and unsuppressed activation of SREBPs, which massively promote lipid synthesis despite stalled secretion and induce full-blown NASH within weeks. Collectively, our data uncovered a fundamental mechanism safe-guarding ER function and integrity, dysfunction of which inflicts a novel stress signal underlying the prevalent cardio-metabolic diseases.

About the Speaker: Dr. Xiao-Wei Chen obtained his BS and BA from the Peking University, and completed his Ph.D. training with Dr. Alan Saltiel on metabolic biology at the University of Michigan. He then pursued postdoctoral study on genetics and cardiovascular biology in the laboratory of Dr. David Ginsburg, prior to being recruited back to the Peking University in 2014.  His work focuses on the genetics and cell biology of lipoprotein biology and lipid homeostasis, particularly a receptor-mediated export program for the lipoproteins. He is the recipient of the Young Investigator Award from the Chinese American Diabetes Association and Special Recognition Award from the Society of Heart and Vascular Metabolism, as well as the Earl Stadtman Scholar finalist from the National Institute of Health, USA.
Read more about Professor Xiao-Wei Chen’s work here.