Different distance-dependent effects of ferroptosis propagation (IMAGE)
Caption
Figure 1. Different distance-dependent effects of ferroptosis propagation. Top: localized propagation spreads from initiator cells to direct neighboring bystander cells in a manner that requires cell-cell adhesions. Such “contact-dependent propagation” may proceed stepwise from initiator to bystander cells, provided that cells are permissive to receive and amplify incoming propagative signals. Right cells show possible bystander cells that are non-permissive for propagation, which would terminate cell death waves. Potential non-permissive states could include high antioxidant capacity, low reactive oxygen species or iron, and low PUFA content of membranes. Bottom: long-range propagation can transmit ferroptotic death in a manner that does not require cell-cell adhesions and can spread between cells spaced at least 100 microns apart. Such “contact-independent propagation” may also require bystander cells that are in a permissive state. Long-range propagation may also involve sensitization of bystander cells to death at increasing distances. Right cells show similar non-permissive states as in top row. PUFA: polyunsaturated fatty acid; ROS: reactive oxygen species.
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© Saloni K. Hombalkar,Jyotirekha Das,Michael Overholtzer * 2026. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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