Ferroptosis: mechanisms, therapeutics, and diet
Ferroptosis is a form of cell death driven by iron-dependent oxidation of specific lipids that and was first reported in the Stockwell Lab in 2012. Our ongoing research in ferroptosis seeks to define how cells die during ferroptosis, key regulators of ferroptosis, and how ferroptosis can be harnessed for therapeutic benefit through pharmacological and dietary interventions.
Ferroptosis has been implicated in numerous diseases, as shown in the figure above. In our ongoing research, we are examining the mechanisms by which ferroptosis contributed to several of these diseases, and how pharmacological and dietary induction or inhibition of ferroptosis can be therapeutically beneficial in specific contexts.
One of the methods we use to discover regulators and treatments for modulating ferroptosis is to image the process of ferroptosis in cells. In the image shown, HT-1080 fibrosarcoma cells were treated with a compound that induces ferroptosis, and transferrin receptor 1 (TfR1) detected by fluorescence as a marker of ferroptosis. This allows us to identify compounds and genes that can enhance or suppress this type of cell death. In another approach, we examining why some cancers are addicted to blocking ferroptosis by up regulating coenzyme Q10 and how this can be leveraged for therapeutic benefit. We are also developing new ways of triggering ferroptosis in various cancers, and developing ways to harness the immune system to amplify the anti-cancer effects of ferroptosis.
