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Title: How do different lipid peroxidation mechanisms contribute to ferroptosis?
Lipid peroxidation is the driver of ferroptotic cell death. However, nonconjugated and conjugated polyunsaturated fatty acids potentiate ferroptosis differently, while some isoprenoid-derived lipids inhibit ferroptosis despite being highly oxidizable. In this perspective, we propose that different oxidation mechanisms and products contribute to the discrepancies in the lipids’ potency in modulating ferroptosis. We first discuss the relative reactivities of various lipids toward two rate-determining free radical propagating mechanisms, hydrogen atom transfer (HAT) and peroxyl radical addition (PRA), and the resulting differential product profiles. We then discuss the role and regulation of lipid peroxidation in ferroptosis and the potential contributions of different oxidation products, such as truncated lipids and lipid electrophiles, from HAT and PRA mechanisms to the execution of ferroptosis. Lastly, we offer our perspective on the remaining questions to fully understand the process from lipid peroxidation to ferroptosis.  more » « less
Award ID(s):
1664851
PAR ID:
10485387
Author(s) / Creator(s):
;
Publisher / Repository:
Cell Press
Date Published:
Journal Name:
Cell Reports Physical Science
Volume:
4
Issue:
12
ISSN:
2666-3864
Page Range / eLocation ID:
101683
Subject(s) / Keyword(s):
ferroptosis, lipid peroxidation, conjugated polyunsaturated fatty acids, lipid electrophile, peroxyl radical addition, hydrogen atom transfer
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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