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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/111725
Título

JNK interaction with Sab mediates ER stress induced inhibition of mitochondrial respiration and cell death

AutorWin, Sanda; Than, Tinaung; Fernández-Checa, José C. ; Kaplowitz, Neil
Palabras clavepoptosis
HeLa cells
Signal transduction
Oxidative stress
Reactive oxygen species
Hepatocytes
Fecha de publicación9-ene-2014
EditorNature Publishing Group
CitaciónCell Death & Disease 5(1): e989 (2014)
ResumenOur aim was to better understand the mechanism and importance of sustained c-Jun N-terminal kinase (JNK) activation in endoplasmic reticulum (ER) stress and effects of ER stress on mitochondria by determining the role of mitochondrial JNK binding protein, Sab. Tunicamycin or brefeldin A induced a rapid and marked decline in basal mitochondrial respiration and reserve-capacity followed by delayed mitochondrial-mediated apoptosis. Knockdown of mitochondrial Sab prevented ER stress-induced sustained JNK activation, impaired respiration, and apoptosis, but did not alter the magnitude or time course of activation of ER stress pathways. P-JNK plus adenosine 5'-triphosphate (ATP) added to isolated liver mitochondria promoted superoxide production, which was amplified by addition of calcium and inhibited by a blocking peptide corresponding to the JNK binding site on Sab (KIM1). This peptide also blocked tunicamycin-induced inhibition of cellular respiration. In conclusion, ER stress triggers an interaction of JNK with mitochondrial Sab, which leads to impaired respiration and increased mitochondrial reactive oxygen species, sustaining JNK activation culminating in apoptosis.
Versión del editorhttp://dx.doi.org/10.1038/cddis.2013.522
URIhttp://hdl.handle.net/10261/111725
DOI10.1038/cddis.2013.522
Identificadoresdoi: 10.1038/cddis.2013.522
issn: 2041-4889
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