IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Nuclear-Mitochondrial Shuttling of Cyclophilin A Protects Cells from Apoptosis
Autor/es:
LAGADARI M; DANERI-BECERRA C; VALERIAS B; GALLO LUCIANA I.; GALIGNIANA M.
Lugar:
Les Diablerets
Reunión:
Congreso; The 6th International Conference on the Hsp90 Chaperone Machine; 2012
Institución organizadora:
Hsp90.org
Resumen:
In previous studies, we demonstrated that the Hsp90-binding immunophilin FKBP51 is a mitochondrial factor with antiapoptotic properties. During those studies, we detected in mitochondria the unexpected presence of other immunophilin, the 17-kDa cyclophilin A (CyPA). Here we report that CyPA colocalizes in several cell types (Hek293T, Jurkat, L929, L1, N2a, HeLa) with the mitochondrial marker MitoTracker and with immunofluorescence assays against cytochrome-c, COX-IV or Tom-20. CyPA was also Western-blotted in extracts of rat liver mitochondria isolated by biochemical fractionation. CyPA moved from mitochondria to nuclei when cells were exposed to oxidants, a property already described for FKBP51. However, CyPA moves at a slower rate than FKBP51 since it reaches the nuclei after 4 h of stimulation (versus 15-20 min for FKBP51). Upon washing out the stimulus, CyPA cycled-back to cytoplasm in a CRM-1-independent manner. Both the mitochondrial localization and the nuclear-mitochondrial shuttling are independent of the peptidylprolyl-isomerase activity since a CyPA mutant (H126Q) lacking enzymatic activity showed exactly the same properties. Overexpression of CyPA protected cells from apoptosis after exposure to H2O2 or saturosporine, as it was judged by their picnotic nuclei, the orange green test, binding of annexin-V, and procaspase-3 cleavage. CyPA nuclear translocation was not related to ERK activation since it also takes place when ERK phosphorylation was inhibited by UO126 or staurosporine itself. In summary, we discovered a novel subcellular localization for CyPA and postulate that its nuclear-mitochondrial trafficking relates directly with its antiapoptotic action, which seems not to require the peptidylprolyl-isomerase activity.