Lipids@Wayne will host our next seminar on Wednesday, Oct. 16^th. All are welcome to attend this free event. Pizza will be provided starting at 3:45pm. We hope to see you there!

 

We encourage in-person attendance, but a Zoom link is available upon request by emailing lipids@wayne.edu

 

Date: Wednesday, October 16th, 2024

Time: 4:00 - 5:00 pm (pizza gathering starts at 3:45)

Location: 1177 Biological Sciences Building

Speaker: Mike Lange, Ph.D. (Postdoctoral Fellow - Olzmann lab, UC Berkeley)

Talk Title: Protecting Stored Lipids From Damage: Ferroptosis Suppressor Protein 1 Prevents Lipid Peroxidation In Lipid Droplets

Abstract: 

Lipids are crucial for cellular function but their susceptibility to damage such as peroxidation, can have adverse effects on cellular wellbeing. Cells deploy diverse lipid quality control mechanisms to prevent the buildup of toxic oxidized lipids. Loss of lipid quality control, particularly on phospholipids in the plasma membrane, results in the catastrophic loss of membrane integrity leading to ferroptosis – a lipid peroxidation-dependent cell death modality.

 

Beyond membranes, lipids can form lipid droplets, organelles that consist of hydrophobic lipids such as triglycerides and steryl esters. Lipid droplets facilitate regulated lipid storage and release, thereby ensuring safe lipid metabolism in tissues such as adipose and liver, particularly under conditions of lipid overload. Dysregulation of lipid droplet levels is associated with pathological conditions such as obesity or fatty liver disease. Despite their importance, the existence of lipid quality control mechanisms that safeguard lipid droplets from damage remains uncertain. Furthermore, it is unknown what the consequences of lipid droplet damage are on cellular health.

 

We have identified the first lipid droplet quality control system executed by ferroptosis suppressor protein 1 (FSP1), a protein previously recognized as one of the essential membrane lipid quality control systems. Using chemical biology tools in genome-edited cancer cell lines, we found FSP1 bound to lipid droplets protects cells from lipid peroxidation-induced death. In vitro reconstitution biochemistry, combined with lipidomics and epilipidomics analyses, shows that lipid droplet resident FSP1 acts as a coenzyme Q10 reductase, locally generating the antioxidant ubiquinol, thus preventing lipid droplet damage. This marks the first description of a lipid droplet quality control system, and we are currently investigating how this novel pathway is involved in the disease pathogenesis of dysregulated metabolically active tissues such as adipose tissue during obesity.