INVESTIGADORES
GALIGNIANA Mario Daniel
congresos y reuniones científicas
Título:
Nuclear-Mitochondrial Shuttling of Cyclophilin A Protects Cells from Apoptosis
Autor/es:
LAGADARI M, DANERI-BECERRA C, VALEIRAS B, GALLO LI, GALIGNIANA M
Lugar:
Les Diablerets
Reunión:
Congreso; The 6 th. International Conference on the Hsp90-Chaperone Machine; 2012
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.