In a recent study published in Cell, Qiu et al. unveil a critical role for a specific lipid class, phosphatidylcholines containing two polyunsaturated fatty acyl tails (PC-PUFA2s), in controlling ferroptosis, an iron-dependent form of cell death resulting from excessive lipid peroxidation.

While phospholipids with a single polyunsaturated fatty acyl tail (PL-PUFA1s) have been considered the driving force behind ferroptosis, the researchers found that PC-PUFA2s significantly accumulate upon fatty acid or phospholipid treatments, which correlates with cancer cell sensitivity to ferroptosis.

PC-PUFA2s interact with the mitochondrial electron transport chain, generating reactive oxygen species (ROS) that initiate lipid peroxidation. Mitochondria-targeted antioxidants protected cells from lipid peroxidation, PC-PUFA2-induced mitochondrial ROS, and cell death.

The study reveals that PC-PUFA2s are key drivers of ferroptosis, shedding light on how free polyunsaturated fatty acids promote ferroptosis, how mitochondria promote ferroptosis, and why monounsaturated fatty acids suppress ferroptosis. This research highlights the importance of PC-PUFA2s in regulating ferroptosis sensitivity, with implications for understanding the basic biology of ferroptosis and its potential as a therapeutic target in various diseases.

This study used an Aurora Ultimate CSI 25×75 C18 UHPLC column, enabling high-quality proteomics data acquisition.

Publication
Cell

Authors

Qiu et al.

Title

Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis