Association of fission proteins with mitochondrial raft-like domains.
It was shown that receptor-mediated apoptosis involves a cascade of subcellular events including alterations of mitochondria. Loss of mitochondrial membrane potential that follows death receptor ligation allows the release of apoptogenic factors that result in apoptosis execution. Further important mitochondrial changes have been observed in this regard: mitochondrial remodeling and fission that appear as prerequisites for the occurrence of the cell death program. As it was observed that lipid rafts, glycosphingolipid-enriched structures, can participate in the apoptotic cascade being recruited to the mitochondria under receptor-mediated proapoptotic stimulation, we decided to analyze the possible implication of these microdomains in mitochondrial fission. We found that molecules involved in mitochondrial fission processes are associated with these domains. In particular, although hFis1 was constitutively included in mitochondrial raft-like domains, dynamin-like protein 1 was recruited to these domains on CD95/Fas triggering. Accordingly, the disruption of rafts, for example, by inhibiting ceramide synthase, leads to the impairment of fission molecule recruitment to the mitochondria, reduction of mitochondrial fission and a significant reduction of apoptosis. We hypothesize that under apoptotic stimulation the recruitment of fission-associated molecules to the mitochondrial rafts could have a role in the morphogenetic changes leading to organelle fission.
Ciarlo
L
L
Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Rome, Italy.
Manganelli
V
V
Garofalo
T
T
Matarrese
P
P
Tinari
A
A
Misasi
R
R
Malorni
W
W
Sorice
M
M
D017209:Apoptosis; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D034281:Dynamins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037341:Fumonisins / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000032:analysis; D005732:Gangliosides / Q000032:analysis; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008928:Mitochondria / Q000648:ultrastructure*; D051336:Mitochondrial Membranes / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D017830:Octoxynol; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D034622:RNA Interference; D019014:fas Receptor / Q000378:metabolism
D004791:Enzyme Inhibitors; C476525:FIS1 protein, human; D037341:Fumonisins; D005732:Gangliosides; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D019014:fas Receptor; C056933:fumonisin B1; C026226:ganglioside, GD3; D017830:Octoxynol; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins