Pedrera, Lohans, Espiritu, Rafael A., Ros, Uris, Weber, Josephine, Schmitt, Anja, Stroh, Jenny, Hailfinger, Stephan, von Karstedt, Silvia ORCID: 0000-0002-7816-5919 and Garcia-Saez, Ana J. . Ferroptotic pores induce Ca2+ fluxes and ESCRT-III activation to modulate cell death kinetics. Cell Death Differ.. LONDON: SPRINGERNATURE. ISSN 1476-5403

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Abstract

Ferroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca2+ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of a few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca2+ fluxes during ferroptosis induce the activation of the ESCRT-III-dependent membrane repair machinery, which counterbalances the kinetics of cell death and modulates the immunological signature of ferroptosis. Our findings with ferroptosis provide a unifying concept that sustained increase of cytosolic Ca2+ prior to plasma membrane rupture is a common feature of regulated types of necrosis and position ESCRT-III activation as a general protective mechanism in these lytic cell death pathways.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pedrera, LohansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espiritu, Rafael A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ros, UrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, JosephineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitt, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroh, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hailfinger, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Karstedt, SilviaUNSPECIFIEDorcid.org/0000-0002-7816-5919UNSPECIFIED
Garcia-Saez, Ana J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-307834
DOI: 10.1038/s41418-020-00691-x
Journal or Publication Title: Cell Death Differ.
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 1476-5403
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MEMBRANE REPAIR; CALCIUM; NECROPTOSIS; MLKL; MECHANISMS; DOWNSTREAM; METABOLISM; PYROPTOSIS; EXECUTION; CHANNELSMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/30783

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