A review titled "Ferroptosis spreading through propagative signals" was published on June 9, 2026, in the journal EXO – Beyond the Cell. The review evaluates how ferroptosis, an iron-dependent form of cell death, may spread through tissues via propagation.
The review was authored by Saloni K. Hombalkar, Jyotirekha Das, and Michael Overholtzer. Ferroptosis has primarily been studied as a cell-autonomous process in which individual cells die following the accumulation of iron-driven lipid peroxidation. Observations from experimental systems indicate that ferroptosis may propagate between cells and travel through tissues in wave-like patterns.
Propagation may explain why ferroptosis often appears as synchronized, large-scale cell death rather than isolated individual cell death. Ferroptotic death can occur as synchronized waves where neighboring cells undergo ferroptosis sequentially. This sequential cell death has been observed in cultured cells, kidney tubules, and during normal muscle patterning in developing avian limbs.
The review synthesizes findings from studies of kidney injury, cancer models, and developmental systems. Localized propagation occurs between directly contacting cells and depends on cell–cell adhesions. Long-range propagation can occur across distances exceeding 100 micrometers without requiring direct cellular contact.
Lipid peroxides are identified as likely candidates for the propagative signals that drive ferroptotic damage. Multiple studies demonstrate that ferroptosis propagation can be blocked by lipid radical-trapping antioxidants after death waves begin. Elevated iron levels have been detected at the advancing fronts of propagating death waves, and iron chelators can suppress the spreading of ferroptosis.
A proposed model suggests damaged cells release lipid peroxide-containing membrane structures or lysosome-derived vesicles that neighboring cells can absorb. Absorption of these released structures may trigger further ferroptosis in neighboring cells. Iron-loaded ferritin transported through extracellular vesicles may also contribute to the transmission of ferroptotic signals. The authors suggest that researchers should consider ferroptosis at the level of cell populations and tissues rather than solely within individual cells.