Open AccessFerroptosis occurs through an osmotic mechanism and propagates independently of cell rupture
Author(s) -
Michelle Riegman,
Liran Sagie,
Chen Galed,
Tom Levin,
Noah Steinberg,
Scott J. Dixon,
Ulrich Wiesner,
Michelle S. Bradbury,
Philipp Niethammer,
Assaf Zaritsky,
Michael Overholtzer
Publication year - 2020
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-020-0565-1
Subject(s) - pyroptosis , programmed cell death , microbiology and biotechnology , gpx4 , necroptosis , cell , apoptosis , chemistry , intracellular , lipid peroxide , cell membrane , autophagy , cell damage , biology , glutathione , oxidative stress , biochemistry , lipid peroxidation , glutathione peroxidase , enzyme
Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis 1,2 . Although other types of necrotic death such as pyroptosis and necroptosis are mediated by active mechanisms of execution 3-6 , ferroptosis is thought to result from the accumulation of unrepaired cell damage 1 . Previous studies have suggested that ferroptosis has the ability to spread through cell populations in a wave-like manner, resulting in a distinct spatiotemporal pattern of cell death 7,8 . Here we investigate the mechanism of ferroptosis execution and discover that ferroptotic cell rupture is mediated by plasma membrane pores, similarly to cell lysis in pyroptosis and necroptosis 3,4 . We further find that intercellular propagation of death occurs following treatment with some ferroptosis-inducing agents, including erastin 2,9 and C' dot nanoparticles 8 , but not upon direct inhibition of the ferroptosis-inhibiting enzyme glutathione peroxidase 4 (GPX4) 10 . Propagation of a ferroptosis-inducing signal occurs upstream of cell rupture and involves the spreading of a cell swelling effect through cell populations in a lipid peroxide- and iron-dependent manner.