2022
DOI: 10.1039/d2sc00525e
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Live-cell imaging reveals impaired detoxification of lipid-derived electrophiles is a hallmark of ferroptosis

Abstract: The central mechanism in ferroptosis linking lipid hydroperoxide accumulation with cell death remains poorly understood. Although lipid hydroperoxides are known to break down to reactive lipid-derived electrophiles (LDEs), the ability...

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Cited by 18 publications
(18 citation statements)
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References 58 publications
(105 reference statements)
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“…Together, these findings highlight the importance of lipid-derived electrophiles in the execution of ferroptosis. In fact, impaired detoxification of lipid-derived electrophiles was recently suggested to be a hallmark of ferroptosis . Thus, we hypothesize that the accumulation of the highly toxic electrophilic aldehydes contributes to the high potency of conjugated PUFAs in potentiating ferroptosis.…”
Section: Discussionmentioning
confidence: 74%
See 1 more Smart Citation
“…Together, these findings highlight the importance of lipid-derived electrophiles in the execution of ferroptosis. In fact, impaired detoxification of lipid-derived electrophiles was recently suggested to be a hallmark of ferroptosis . Thus, we hypothesize that the accumulation of the highly toxic electrophilic aldehydes contributes to the high potency of conjugated PUFAs in potentiating ferroptosis.…”
Section: Discussionmentioning
confidence: 74%
“…In fact, impaired detoxification of lipid-derived electrophiles was recently suggested to be a hallmark of ferroptosis. 110 Thus, we hypothesize that the accumulation of the highly toxic electrophilic aldehydes contributes to the high potency of conjugated PUFAs in potentiating ferroptosis. Indeed, pathway analysis from RNA-seq results suggests increased protein damage and ER stress in cells treated with conjugated PUFAs ( Figure 6 ).…”
Section: Discussionmentioning
confidence: 97%
“…Together, these findings highlight the importance of lipid-derived electrophiles in the execution of ferroptosis. In fact, impaired detoxification of lipid-derived electrophiles was recently suggested to be a hallmark of ferroptosis (105). Thus, we hypothesize that the accumulation of the highly toxic electrophilic aldehydes contributes to the high potency of conjugated PUFAs in potentiating ferroptosis.…”
Section: Discussionmentioning
confidence: 71%
“…Iron is a critical inducer of ferroptosis, without which the cell death pathway may be inhibited, whereas an exogenous supply of iron enhances ferroptosis [ 67 , 68 ]. Unrestrained lipid peroxidation of mainly the PUFA in the membrane bilayers is one of the hallmarks for ferroptosis [ 69 ]. The accumulation of lipid peroxides in ferroptosis is iron dependent and can be pharmacologically inhibited by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin, vitamin E, and butylated hydroxytoluene) [ 7 ].…”
Section: Ferroptosis: Iron- and Lipid-peroxidation-dependent Cell Deathmentioning
confidence: 99%