Abstract
Subcellular organelles such as mitochondria, endoplasmic reticulum (ER) and the Golgi complex are involved in the progression of the cell death programme. We report here that soon after ligation of Fas (CD95/Apo1) in type II cells, elements of the Golgi complex intermix with mitochondria. This mixing follows centrifugal dispersal of secretory membranes and reflects a global alteration of membrane traffic. Activation of apical caspases is instrumental for promoting the dispersal of secretory organelles, since caspase inhibition blocks the outward movement of Golgi-related endomembranes and reduces their mixing with mitochondria. Caspase inhibition also blocks the FasL-induced secretion of intracellular proteases from lysosomal compartments, outlining a novel aspect of death receptor signalling via apical caspases. Thus, our work unveils that Fas ligand-mediated apoptosis induces scrambling of mitochondrial and secretory organelles via a global alteration of membrane traffic that is modulated by apical caspases.
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Abbreviations
- E64:
-
trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane
- HPA:
-
Helix pomatia agglutinin
- IETD:
-
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
- IVM:
-
intensified video microscopy
- MTR:
-
Mitotracker®
- RB:
-
modified Ringer buffer
- TEM:
-
transmission electron microscopy
- z-VAD:
-
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
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Acknowledgements
We thank the whole Bioimaging facility of the University of Manchester for the support provided and Martin Lowe and Saska Ivanova for their inputs. RK acknowledges Grant NIH/NHLBI (HL080192) and WM of grants from Ministero della Sanita'. MDE research is supported by BBSRC Grant BB/C508469.
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Ouasti, S., Matarrese, P., Paddon, R. et al. Death receptor ligation triggers membrane scrambling between Golgi and mitochondria. Cell Death Differ 14, 453–461 (2007). https://doi.org/10.1038/sj.cdd.4402043
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DOI: https://doi.org/10.1038/sj.cdd.4402043
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