Description:

The Department of Biochemistry & Molecular Genetics presents:

James A. Olzmann
Associate Professor
Departments of Molecular & Cell Biology and Nutritional Sciences & Toxicology
University of California, Berkeley 

Presentation:

"Mechanisms of lipid quality control and ferroptosis"

 Abstract:

The research in the Olzmann lab aims to elucidate the mechanisms that govern cellular lipid homeostasis, including neutral lipid storage in lipid droplets and lipid damage leading to lipotoxic cell death. In this seminar, Dr. Olzmann will discuss recent advances in our understanding of the cell biology that underlies lipid quality control and ferroptosis. Ferroptosis is a recently discovered form of non-apoptotic cell death that involves the iron-dependent accumulation of oxidatively damaged phospholipids (i.e., phospholipid hydroperoxides). To understand the mechanisms that cells employ to combat lipid damage, the Olzmann lab employs a synthetic lethal CRISPR screening platform to discover new pathways that regulate the cellular response to oxidatively damaged lipids and ferroptosis. For example, employing this approach, they discovered that the CoQ oxidoreductase FSP1 functions as a ferroptosis resistance factor by generating the reduced form of CoQ (i.e., ubiquinol), which acts as a lipophilic antioxidant to suppress the propagation of lipid peroxides. Employing similar approaches, they also discovered rewiring of selenium metabolism in cancer cells that results in a vulnerability to ribosome stalling and collisions during GPX4 translation and in an increased ferroptosis sensitivity. Together, these findings highlight the power of genetic discovery approaches as a powerful strategy to uncover therapeutically relevant mechanisms that regulate oxidative lipid damage and ferroptosis in health and disease.

Hosts: Dr. Issam Ben-Sahra, Assistant Professor of Biochemistry and Molecular Genetics and Dr. Navdeep S. Chandel, Professor of Medicine (Pulmonary and Critical Care) and Biochemistry and Molecular Genetics