What is it about?

Over the last decade, the cell death mechanism ferroptosis has emerged as a promising opportunity in our fight against both cancer and neurodegenerative disease. Research efforts to accurately map the ferroptosis pathway are essential in the identification of appropriate molecular targets for therapeutic intervention. Here, through a fluorescence microscopy-based investigation, we identified that a highly reactive class of downstream lipid oxidation products, called lipid-derived electrophiles (LDEs), can mediate inhibition of specific plasma membrane protein channels. Considering LDEs can react with many types of proteins during ferroptosis, our functional study identifies LDEs as important executors of cell damage during ferroptotic cell death.

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Why is it important?

Our study identifies lipid-derived electrophiles as mediators of protein damage during ferroptosis. Not only does this finding improve our understanding of the molecular steps of this recently discovered cell death pathway, but it sets the stage for the development of ferroptosis-based therapies that target LDE metabolism.


In this article, we were able to build on years of fluorescent probe and live-cell imaging research in our group. It is exciting to see that a research project that truly began before "ferroptosis" was even coined has now led to an improved understanding of this cell death pathway.

Antonius Van Kessel
McGill University

Read the Original

This page is a summary of: Lipid-derived electrophiles inhibit the function of membrane channels during ferroptosis, Proceedings of the National Academy of Sciences, May 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2317616121.
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