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Title: Ferroptosis induces membrane blebbing in placental trophoblasts
Authors: Kajiwara, Kazuhiro
Beharier, Ofer
Chng, Choon-Peng
Goff, Julie P.
Ouyang, Yingshi
St Croix, Claudette M.
Huang, Changjin
Kagan, Valerian E.
Hsia, K. Jimmy
Sadovsky, Yoel
Keywords: Engineering::Chemical engineering
Issue Date: 2022
Source: Kajiwara, K., Beharier, O., Chng, C., Goff, J. P., Ouyang, Y., St Croix, C. M., Huang, C., Kagan, V. E., Hsia, K. J. & Sadovsky, Y. (2022). Ferroptosis induces membrane blebbing in placental trophoblasts. Journal of Cell Science, 135(5), jcs255737-.
Project: M4082428.050
Journal: Journal of Cell Science
Abstract: Ferroptosis is a regulated, non-apoptotic form of cell death, characterized by hydroxy-peroxidation of discrete phospholipid hydroperoxides, particularly hydroperoxyl (Hp) forms of arachidonoyl- and adrenoyl-phosphatidylethanolamine, with a downstream cascade of oxidative damage to membrane lipids, proteins and DNA, culminating in cell death. We recently showed that human trophoblasts are particularly sensitive to ferroptosis caused by depletion or inhibition of glutathione peroxidase 4 (GPX4) or the lipase PLA2G6. Here, we show that trophoblastic ferroptosis is accompanied by a dramatic change in the trophoblast plasma membrane, with macro-blebbing and vesiculation. Immunofluorescence revealed that ferroptotic cell-derived blebs stained positive for F-actin, but negative for cytoplasmic organelle markers. Transfer of conditioned medium that contained detached macrovesicles or co-culture of wild-type target cells with blebbing cells did not stimulate ferroptosis in target cells. Molecular modeling showed that the presence of Hp-phosphatidylethanolamine in the cell membrane promoted its cell ability to be stretched. Together, our data establish that membrane macro-blebbing is characteristic of trophoblast ferroptosis and can serve as a useful marker of this process. Whether or not these blebs are physiologically functional remains to be established.
ISSN: 0021-9533
DOI: 10.1242/jcs.255737
Rights: © 2021 The Author(s). All rights reserved. This paper was published by The Company of Biologists Ltd in Journal of Cell Science and is made available with permission of The Author(s).
Fulltext Permission: embargo_20230331
Fulltext Availability: With Fulltext
Appears in Collections:MAE Journal Articles
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