Ferroptosis propagates to neighboring cells via cell-cell contacts

Roeck, B. F.; Vorndran, M. R. H.; Garcia-Saez, A. J.

doi:10.1101/2023.03.24.534081

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bioRxiv · 10.1101/2023.03.24.534081

Ferroptosis propagates to neighboring cells via cell-cell contacts

Roeck, B. F.·Vorndran, M. R. H.·Garcia-Saez, A. J.

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Abstract

Ferroptosis is an iron-dependent form of regulated cell death characterized by accumulation of peroxidized lipids and plasma membrane disruption, whose molecular mechanism of execution remains poorly understood. Here, we developed a new optogenetic system, Opto-GPX4Deg, for light-induced degradation of the lipid reducing protein GPX4, which allows controlled ferroptosis induction with high precision in time and space. By using Opto-GPX4Deg to study cell death dynamics within the cellular population, we found that lipid peroxidation, followed by ferroptotic death, spread to neighboring cells in a distance-dependent manner. Remarkably, ferroptosis propagation showed a strong dependency on cell confluence and preferentially affected adjacent cells. Our findings establish cell death propagation as a feature of ferroptosis and provide new understanding of the mechanism involved.

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Roeck, B. F., Vorndran, M. R. H., Garcia-Saez, A. J.. 2023-03-24. Ferroptosis propagates to neighboring cells via cell-cell contacts. https://doi.org/10.1101/2023.03.24.534081

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