Speaker: Marcus Conrad, Research Director, Institute of Metabolism and Cell Death, Molecular Targets and Therapeutics Center, Helmholtz Munich, Germany

Time: 16:00-17:00 p.m., Aug 26, 2024, GMT+8

Venue: Rm B117, Research Complex #2, PKU

Abstract: 

Ferroptosis is a metabolic form of regulated cell death characterized by an iron-dependent oxidative destruction of cellular membranes. Ferroptosis emerges as the underlying cause of several degenerative diseases and presents a pharmacologically tractable vulnerability to eradicate difficult-to-treat cancers. Years before the term "ferroptosis" was coined, we had shown that glutathione peroxidase 4 (GPX4), by preventing unrestrained phospholipid peroxidation in cells and mice, controls a new type of non-apoptotic cell death, now known as ferroptosis. Using genetic suppressor screens, we further introduced ferroptosis suppressor pro-tein-1 (FSP1) as the second ferroptosis surveillance system. The anti-ferroptotic role of FSP1 is based on the NAD(P)H dependent reduction of extra-mitochondrial coenzyme Q10, thereby halting uncontrolled lipid per-oxidation and ferroptosis. Besides, FSP1 constitutes the long sought-after, warfarin-resistant vitamin K reduc-tase in the canonical vitamin K cycle, thus linking vitamin K biology and ferroptosis. We recently reported the first in vivo active FSP1 inhibitor, icFSP1, which induces phase separation of FSP1 prior to cancer cell death induction. Ongoing studies are therefore geared towards understanding the in vivo relevance of these systems in ferroptosis control and their pharmacological tractability as the basis for developing new pharmacotherapies for ferroptosis-related diseases including neurodegeneration and cancer.

Source: College of Future Technology, PKU