Excessive Phospholipid Peroxidation Distinguishes Ferroptosis from Other Cell Death Modes Including Pyroptosis

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Oct 28

PMID 33110056

Citations 104

Authors

Bartosz Wiernicki

Hanne Dubois

Yulia Y Tyurina

Behrouz Hassannia

Hulya Bayir

Valerian E Kagan

Peter Vandenabeele

Andy Wullaert

Tom Vanden Berghe

Affiliations

Soon will be listed here.

Abstract

Lipid peroxidation (LPO) drives ferroptosis execution. However, LPO has been shown to contribute also to other modes of regulated cell death (RCD). To clarify the role of LPO in different modes of RCD, we studied in a comprehensive approach the differential involvement of reactive oxygen species (ROS), phospholipid peroxidation products, and lipid ROS flux in the major prototype modes of RCD viz. apoptosis, necroptosis, ferroptosis, and pyroptosis. LC-MS oxidative lipidomics revealed robust peroxidation of three classes of phospholipids during ferroptosis with quantitative predominance of phosphatidylethanolamine species. Incomparably lower amounts of phospholipid peroxidation products were found in any of the other modes of RCD. Nonetheless, a strong increase in lipid ROS levels was detected in non-canonical pyroptosis, but only during cell membrane rupture. In contrast to ferroptosis, lipid ROS apparently was not involved in non-canonical pyroptosis execution nor in the release of IL-1β and IL-18, while clear dependency on CASP11 and GSDMD was observed. Our data demonstrate that ferroptosis is the only mode of RCD that depends on excessive phospholipid peroxidation for its cytotoxicity. In addition, our results also highlight the importance of performing kinetics and using different methods to monitor the occurrence of LPO. This should open the discussion on the implication of particular LPO events in relation to different modes of RCD.

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