Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis.
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.
Pubmed ID: 38366593 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- UQCRFS1/RISP Antibody (RRID:AB_2922784)
- ACP/NDUFAB1 (E2V9B) Rabbit mAb (RRID:AB_3086728)
- IRDye 680RD Goat anti-Rabbit IgG (RRID:AB_10956166)
- IRDye 800CW Goat anti-Mouse IgG (RRID:AB_621842)
- Goat Anti-Mouse IgG (H+L) Highly Cross-adsorbed Antibody, Alexa Fluor ?? 594 Conjugated (RRID:AB_2534091)
- Goat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ Plus 405 (RRID:AB_2890548)
- Goat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ Plus 488 (RRID:AB_2633275)
- NDUFS1 (E4K3E) Rabbit mAb (RRID:AB_3086727)
- alpha Tubulin (DM1A) (RRID:AB_628412)
- LAMP1 (D2D11) XP Rabbit Antibody (RRID:AB_2687579)
- Mouse Anti-Giantin Monoclonal Antibody, Unconjugated, Clone 9B6 (RRID:AB_880195)
- Anti-COX IV antibody [mAbcam33985] - Mitochondrial Marker (RRID:AB_879754)
- Calnexin - ER membrane marker antibody (RRID:AB_2069006)
- Pan-Actin (D18C11) Rabbit mAb (RRID:AB_10998774)
- Rabbit Anti-GAPDH Polyclonal Antibody, Unconjugated (RRID:AB_307275)
- GADD 153 (B-3) (RRID:AB_627411)
- Purified anti-XBP-1s (RRID:AB_2241744)
- Cleaved Caspase-3 (Asp175) Antibody (RRID:AB_2341188)
- Caspase-3 Antibody (RRID:AB_331439)
- Phospho-MLKL (Ser345) (D6E3G) Rabbit mAb (RRID:AB_2799112)
- Acyl-CoA synthetase long-chain family member 4 (RRID:AB_10843105)
- Glutathione Peroxidase 4 antibody [EPNCIR144] (RRID:AB_10973901)
Associated grants
- Agency: NCI NIH HHS, United States
Id: R35 CA209896
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This is a list of tools and resources that we have found mentioned in this publication.
UQCRFS1/RISP Antibody (antibody)
RRID:AB_2922784
This polyclonal targets UQCRFS1/RISP
View all literature mentionsACP/NDUFAB1 (E2V9B) Rabbit mAb (antibody)
RRID:AB_3086728
This monoclonal targets ACP/NDUFAB1
View all literature mentionsIRDye 680RD Goat anti-Rabbit IgG (antibody)
RRID:AB_10956166
This polyclonal targets IgG
View all literature mentionsIRDye 800CW Goat anti-Mouse IgG (antibody)
RRID:AB_621842
This unknown targets IgG
View all literature mentionsGoat Anti-Mouse IgG (H+L) Highly Cross-adsorbed Antibody, Alexa Fluor ?? 594 Conjugated (antibody)
RRID:AB_2534091
This unknown targets IgG (H+L)
View all literature mentionsGoat anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ Plus 405 (antibody)
RRID:AB_2890548
This polyclonal secondary targets IgG (H+L)
View all literature mentionsGoat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ Plus 488 (antibody)
RRID:AB_2633275
This polyclonal secondary targets IgG (H+L)
View all literature mentionsNDUFS1 (E4K3E) Rabbit mAb (antibody)
RRID:AB_3086727
This recombinant monoclonal targets NDUFS1
View all literature mentionsalpha Tubulin (DM1A) (antibody)
RRID:AB_628412
This monoclonal targets alpha Tubulin (DM1A)
View all literature mentionsLAMP1 (D2D11) XP Rabbit Antibody (antibody)
RRID:AB_2687579
This monoclonal targets LAMP1
View all literature mentionsMouse Anti-Giantin Monoclonal Antibody, Unconjugated, Clone 9B6 (antibody)
RRID:AB_880195
This monoclonal targets Giantin
View all literature mentionsAnti-COX IV antibody [mAbcam33985] - Mitochondrial Marker (antibody)
RRID:AB_879754
This monoclonal targets COX IV
View all literature mentionsCalnexin - ER membrane marker antibody (antibody)
RRID:AB_2069006
This polyclonal targets CANX
View all literature mentionsPan-Actin (D18C11) Rabbit mAb (antibody)
RRID:AB_10998774
This monoclonal targets Pan-Actin (D18C11) Rabbit mAb
View all literature mentionsRabbit Anti-GAPDH Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_307275
This polyclonal targets GAPDH
View all literature mentionsPurified anti-XBP-1s (antibody)
RRID:AB_2241744
This monoclonal targets XBP-1s
View all literature mentionsCleaved Caspase-3 (Asp175) Antibody (antibody)
RRID:AB_2341188
This polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsCaspase-3 Antibody (antibody)
RRID:AB_331439
This polyclonal targets Caspase-3
View all literature mentionsPhospho-MLKL (Ser345) (D6E3G) Rabbit mAb (antibody)
RRID:AB_2799112
This monoclonal targets MLKL
View all literature mentionsAcyl-CoA synthetase long-chain family member 4 (antibody)
RRID:AB_10843105
This monoclonal targets raised against amino acids 623-675 mapping near the C-terminus of ACSL4 of human origin
View all literature mentionsGlutathione Peroxidase 4 antibody [EPNCIR144] (antibody)
RRID:AB_10973901
This monoclonal targets Glutathione Peroxidase 4 antibody [EPNCIR144]
View all literature mentionsCellProfiler Image Analysis Software (data processing software)
RRID:SCR_007358
Software tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
View all literature mentions
