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SIGNALLING AND CELL DEATH

Igniting the spread of ferroptotic cell death

Nature Cell Biology volume 22, pages 1027–1029 (2020)Cite this article

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Ferroptosis is an iron-dependent mode of cell death driven by lipid peroxidation, capable of explosively propagating through a field of cells. Two studies now explore the mechanisms underlying ferroptotic cell death and its spread, as well as its possible in vivo significance, shedding light on some of the burning questions surrounding ferroptosis.

If a cell was an instruction manual, the very last paragraph would delineate a bewildering array of options for its disposal1. For example, the programmed, inflammatory ‘silent’ form of cell death, apoptosis, could be thought of as the equivalent to an instruction to carefully fold and shred the manual before sweeping it tidily into the recycling bin2. This is in stark contrast to the highly inflammatory necrosis, which is thought to be unregulated and could be likened to scrunching up the manual into a paper ball and throwing it haphazardly across the room2. There are subtle, but important, distinctions between unregulated necrosis and regulated necrosis (such as necroptosis)3. Nevertheless, many forms of regulated necrosis whereby cells deliberately instigate a necrotic demise have been identified1. It is becoming increasingly clear that cells contain multiple pathways by which to die to impart one last signal or message to those cells it leaves behind before its ultimate departure4.

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Fig. 1: Cell–cell propagation of ferroptosis is a distinct step from ferroptotic cell lysis.
Fig. 2: Lipid peroxidation is utilised as a long-range communication system to relay inflammatory signals to recruit leukocytes (green), despite the risk of inducing catastrophic spread of ferroptosis.

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  1. Centre for Inflammation Research, University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK

    Andrew J. Davidson & Will Wood

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  1. Andrew J. Davidson
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  2. Will Wood
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Correspondence to Will Wood.

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Davidson, A.J., Wood, W. Igniting the spread of ferroptotic cell death. Nat Cell Biol 22, 1027–1029 (2020). https://doi.org/10.1038/s41556-020-0570-4

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