Abstact
We previously reported that during death receptor-mediated apoptosis, cardiolipin (CL) relocates to the cell surface, where it reacts with autoantibodies from antiphospholipid syndrome sera. Here, we analysed the intracellular distribution of CL and its metabolites during the early phase of cell death signalling triggered by Fas stimulation in U937 cells and mouse liver. We found a redistribution of mitochondrial CL to the cell surface by using confocal microscopy and flow cytometry. Mass spectrometry revealed that CL and its metabolites relocated from mitochondria to other intracellular organelles during apoptosis, with a conversion into non-mitochondrial lipids. Concomitantly, cytosolic Bid relocated to the light membranes comprised in fraction P100, including the plasma membrane and associated vesicular systems. A direct Bid–CL interaction was demonstrated by the observation that CL and monolysoCL coimmunoprecipitated with Bid especially after Fas stimulation, suggesting a dynamic interaction of the protein with CL and its metabolites.
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Abbreviations
- APG:
-
acyl-phosphatidylglycerol
- APS:
-
antiphospholipid syndrome
- CL:
-
cardiolipin
- DAG:
-
diacyl-glycerol
- DCL:
-
di-lysocardiolipin
- ER:
-
endoplasmic reticulum
- LBPA:
-
lyso-bis-phosphatidic acid
- MCL:
-
mono-lysocardiolipin
- MS:
-
mass spectrometry
- NDGA:
-
nordihydroguaiaretic acid
- PC:
-
phosphatidylcholine
- PC-PLC:
-
phosphatidylcholine-specific phospholipase C
- PE:
-
phosphatidylethanolamine
- PG:
-
phosphatidylglycerol
- PGP:
-
phosphatidylglycerol-phosphate
- PI:
-
phosphatidylinositol
- PIP:
-
phosphatidylinositol-phosphate
- PLA-2:
-
phospholipase A2
- PS:
-
phosphatidylserine
- SLBPA:
-
semi-lyso-bis-phosphatidic acid
- SM:
-
sphingomyelin
- TMRE:
-
tetramethyl-rhodamine-ethyl-ester
- z-VAD-FMK:
-
z-Val-Ala-Asp-fluoromethyl ketone
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Acknowledgements
The work in Rome was supported by MIUR, and a grant to M Sorice. Research in Manchester has been sponsored by AICR and Barth Syndrome Foundation, Inc. We warmly thank Simon Gaskell and Caroline Dive for their support and Ying Chen for technical assistance.
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Sorice, M., Circella, A., Cristea, I. et al. Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. Cell Death Differ 11, 1133–1145 (2004). https://doi.org/10.1038/sj.cdd.4401457
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DOI: https://doi.org/10.1038/sj.cdd.4401457
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