Ferroptosis in Human Health and Disease

Fig. 1. Simplified schematic highlighting the main biochemical pathways involved in ferroptosis. GPX4 recruits the antioxidant glutathione to reduce reactive lipid peroxides into lipid alcohols, thus preventing spontaneous ferroptosis induction. Iron catalyzes the initiation and the propagation of the lipid reactive oxygen species (ROS) cascade. FSP1 also suppresses ferroptosis. (Image created using BioRender)

Ferroptosis is an ancestral, non-apoptotic, iron-dependent form of cell death driven by oxidative modifications of membrane phospholipids. These oxidized phospholipids compromise the integrity of critical cell membranes and trigger cell death via mechanisms that are still unclear. Ferroptosis has been implicated in a broad spectrum of pathological disorders, including neurodegenerative diseases, cardiovascular disorders, autoimmune conditions, and microbial infections. Recent studies demonstrated that activated CD8+ T cells can induce ferroptosis in cancer cells, suggesting the intriguing potential role of ferroptosis as part of the body’s natural defense mechanism.

Cancer cells resistant to a wide range of chemo-, targeted- and even immuno-therapies, are particularly susceptible to killing by ferroptosis inducers such as GPX4 inhibitors. Such striking observations underscore why ferroptosis has captured the attention of both academic and pharmaceutical communities. However, in order to realize the full therapeutic potential of ferroptosis-based therapies, it is critical that we first acquire a fundamental understanding of the biochemical and molecular pathways regulating ferroptosis, and its biological roles within physiological contexts. Therefore, our lab will focus on the following key questions:

  1. What makes a cell susceptible to ferroptosis?

  2. How do cells initially sensitive to ferroptosis escape this cell death fate?

  3. What is the impact of ferroptosis induction in specific cell types on the surrounding tissue milieu?

“We stand on the brink of the next great discovery. And that is exciting. Who wouldn’t want to be part of that?”

— Whitney S. Henry