Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Pedrera, Lohans UNSPECIFIED UNSPECIFIED UNSPECIFIED Espiritu, Rafael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ros, Uris UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Stroh, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Hailfinger, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED von Karstedt, Silvia UNSPECIFIED orcid.org/0000-0002-7816-5919 UNSPECIFIED Garcia-Saez, Ana J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MEMBRANE REPAIR; CALCIUM; NECROPTOSIS; MLKL; MECHANISMS; DOWNSTREAM; METABOLISM; PYROPTOSIS; EXECUTION; CHANNELS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30783