Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis Journal Article


Authors: Qiu, B.; Zandkarimi, F.; Bezjian, C. T.; Reznik, E.; Soni, R. K.; Gu, W.; Jiang, X.; Stockwell, B. R.
Article Title: Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis
Abstract: Phospholipids containing a single polyunsaturated fatty acyl tail (PL-PUFA1s) are considered the driving force behind ferroptosis, whereas phospholipids with diacyl-PUFA tails (PL-PUFA2s) have been rarely characterized. Dietary lipids modulate ferroptosis, but the mechanisms governing lipid metabolism and ferroptosis sensitivity are not well understood. Our research revealed a significant accumulation of diacyl-PUFA phosphatidylcholines (PC-PUFA2s) following fatty acid or phospholipid treatments, correlating with cancer cell sensitivity to ferroptosis. Depletion of PC-PUFA2s occurred in aging and Huntington's disease brain tissue, linking it to ferroptosis. Notably, PC-PUFA2s interacted with the mitochondrial electron transport chain, generating reactive oxygen species (ROS) for initiating lipid peroxidation. Mitochondria-targeted antioxidants protected cells from PC-PUFA2-induced mitochondrial ROS (mtROS), lipid peroxidation, and cell death. These findings reveal a critical role for PC-PUFA2s in controlling mitochondria homeostasis and ferroptosis in various contexts and explain the ferroptosis-modulating mechanisms of free fatty acids. PC-PUFA2s may serve as diagnostic and therapeutic targets for modulating ferroptosis. © 2024 Elsevier Inc.
Keywords: controlled study; human tissue; human cell; correlation analysis; reactive oxygen species; reactive oxygen metabolite; aging; lipids; fatty acids; oxidative stress; mitochondria; fatty acid; lipid peroxidation; cell activity; phosphatidylcholine; phospholipids; phospholipid; lipid analysis; ros; brain tissue; huntington chorea; respiratory chain; fatty acid metabolism; acyl coenzyme a; electron transport chain; phosphatidylcholines; polyunsaturated fatty acid; pufa; ferroptosis; human; article; complex i; diacyl-pufa phosphatidylcholine
Journal Title: Cell
Volume: 187
Issue: 5
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2024-02-29
Start Page: 1177
End Page: 1190.e18
Language: English
DOI: 10.1016/j.cell.2024.01.030
PUBMED: 38366593
PROVIDER: scopus
PMCID: PMC10940216
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Xuejun Jiang
    121 Jiang