A powerful cell-protection system prevents cell death by ferroptosis

Abstract

The discovery of a mechanism that guards against a type of cell death celled ferroptosis reveals a system that regenerates a ubiquitous protective component of biological membranes, and might offer a target for anticancer drugs.

Keywords: Cancer; Cell biology; Medical research.

Figure 1 |. A pathway that blocks cell death.

Doll et al. and Bersuker et al. report studies revealing that the FSP1 protein protects human cells from a type of cell death called ferroptosis. Some tumour cells are susceptible to ferroptosis, and this insight about FSP1 is of clinical interest. The finding has also uncovered a previously unknown role for a lipid called ubiquinone. Ubiquinone is found in lipid membranes, including those of an organelle called a mitochondrion, where it aids production of the molecule ATP, the cell’s energy carrier. The authors report that FSP1 targets ubiquinone in the cell membrane to generate a reduced form of the molecule, called ubiquinol (green). Ferroptosis occurs if a form of lipid modification called peroxidation (red) damages the cell membrane; however, ubiquinol inhibits peroxidation and blocks ferroptosis. FSP1 acts independently of another pathway known to block lipid peroxidation and ferroptosis, which requires the proteins GPX4 and glutathione.