@article{7a37f43f13374fc58d21d20b50ba23c9,
title = "ESCRT-III–dependent membrane repair blocks ferroptosis",
abstract = "Ferroptosis is a form of regulated cell death that is triggered by iron accumulation and lipid peroxidation. Although plasma membrane injuries represent an important event in cell death, the impact of membrane repair mechanisms on ferroptosis remains unidentified. Here, we provide the first evidence that membrane repair dependent on endosomal sorting complexes required for transport (ESCRT)-III negatively regulates ferroptotic cancer cell death. The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx. Importantly, the knockdown of CHMP5 or CHMP6 by RNAi sensitizes human cancer cells (e.g., PANC1 and HepG2) to lipid peroxidation-mediated ferroptosis in vitro and in vivo. These findings suggest that ESCRT-III confers resistance to ferroptotic cell death, allowing cell survival under stress conditions.",
keywords = "DAMP, ESCRT, Ferroptosis, Lipid peroxidation, Membrane repair",
author = "Enyong Dai and Lingjun Meng and Rui Kang and Xiaofeng Wang and Daolin Tang",
note = "Funding Information: We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. D.T. was supported by grants from the US National Institutes of Health ( R01CA229275 ) and the American Cancer Society (Research Scholar Grant RSG-16-014-01-CDD [D.T.]). E.D. was supported by the Natural Science Foundation of Jilin Province of China ( 20160101062JC ), the Health Foundation of the Finance Department of Jilin Province ( sczsy201516 ), and the National Natural Science Foundation of China ( 30870355 and 81370497 ). Funding Information: We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. D.T. was supported by grants from the US National Institutes of Health (R01CA229275) and the American Cancer Society (Research Scholar Grant RSG-16-014-01-CDD [D.T.]). E.D. was supported by the Natural Science Foundation of Jilin Province of China (20160101062JC), the Health Foundation of the Finance Department of Jilin Province (sczsy201516), and the National Natural Science Foundation of China (30870355 and 81370497). Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2020",
month = feb,
day = "5",
doi = "10.1016/j.bbrc.2019.11.110",
language = "English (US)",
volume = "522",
pages = "415--421",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",
}