Ferroptosis spreading through propagative signals

Saloni K. Hombalkar

1,2

Jyotirekha Das

Michael Overholtzer

1,2,3,*

*Correspondence to: Michael Overholtzer, Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. E-mail: overhom1@mskcc.org

EXO. 2026;1:202613. 10.70401/EXO.2026.0011

Received: March 07, 2026Accepted: May 26, 2026Published: May 26, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Ferroptosis is a regulated mechanism of cell death caused by the uncontrolled peroxidation of cellular lipids that has an unusual ability to propagate or spread between cells. Here we review studies identifying regulators of ferroptosis propagation to consider a working model that might explain this unusual feature. Recent findings implicating the spread of lipid peroxides and iron suggest that these main catalysts of ferroptosis may also be primary vehicles that can spread death between cells. Experiments revealing localized versus long-range effects of propagation are discussed, as well as sensitizing factors that may expand the propagative potential of death induced by Class II ferroptosis-inducing compounds. As ferroptosis propagation may underlie the loss of large groups of cells in degenerative diseases and may also have a specialized role in normal development, consideration of how ferroptosis can spread through propagative signals may be important for understanding both normal tissue dynamics and disease.

Keywords

Ferroptosis, propagation, lipid peroxidation, iron, lysosome, GPX4, ferritin, erastin

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