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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/112153
Título

Trafficking of ganglioside GD3 to mitochondria by tumor necrosis factor-α

AutorGarcía-Ruiz, Carmen ; Colell Riera, Anna ; Morales, Albert ; Calvo, María Nieves; Enrich, Carlos; Fernández-Checa, José C.
Fecha de publicación27-sep-2002
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónJournal of Biological Chemistry 277(39): 36443-36448 (2002)
ResumenThe interaction of mitochondria with proapoptotic proteins activates apoptosis pathways. Previous findings have identified ganglioside GD3 (GD3) as an emerging apoptotic lipid intermediate that targets mitochondria in response to death signals. Using immunoelectron and laser scanning confocal microscopy, we characterize the trafficking of GD3 to mitochondria in response to tumor necrosis factor-α (TNF-α) in rat hepatocytes. In control hepatocytes, GD3 is present predominantly at the plasma membrane as well as in the endosomal/Golgi network, as verified by its colocalization with the asialoglycoprotein receptor. Following TNF-α exposure, GD3 undergoes a rapid cellular redistribution with a gradual loss from the plasma membrane before its colocalization with mitochondria. This process is mimicked by acidic sphingomyelinase and ionizing radiation but not by neutral sphingomyelinase or staurosporin. TNF-α stimulated the colocalization of GD3 with early and late endosomal markers, Rab 5 and Rab 7, whereas perturbation of plasma membrane cholesterol or actin cytoskeleton or inhibition of glucosylceramide synthase prevented the trafficking of GD3 to mitochondria. Finally, prevention of the TNF-α-stimulated neosynthesis of GD3, cyclosporin A, and latrunculin A or filipin protected sensitized hepatocytes from TNF-α-mediated cell death. Thus, the intracellular redistribution and mitochondrial targeting of GD3 during TNF-α signaling occurs through actin cytoskeleton vesicular trafficking and contributes to TNF-α-mediated hepatocellular cell death.
Versión del editorhttp://dx.doi.org/10.1074/jbc.M206021200
URIhttp://hdl.handle.net/10261/112153
DOI10.1074/jbc.M206021200
Identificadoresdoi: 10.1074/jbc.M206021200
issn: 0021-9258
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