Death receptor ligation triggers membrane scrambling between Golgi and mitochondria.
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.
Ouasti
S
S
Faculty of Life Sciences, The University of Manchester, Stopford Building, Oxford Road, Manchester, UK.
Matarrese
P
P
Paddon
R
R
Khosravi-Far
R
R
Sorice
M
M
Tinari
A
A
Malorni
W
W
Degli Esposti
M
M
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D019169:Jurkat Cells; D008024:Ligands; D008247:Lysosomes / Q000201:enzymology; D008928:Mitochondria / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
C491901:FAS protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D053218:Receptors, Death Domain; D019014:fas Receptor; D010447:Peptide Hydrolases; D020169:Caspases