Cyclophilin A is a mitochondrial factor that forms complexes with p23. Correlative evidence for an antiapoptotic action

DANERI-BECERRA C, ; VALEIRA B,; GALLO L,; LAGADARI M,; GALIGNIANA MD

JOURNAL OF CELL SCIENCE

COMPANY OF BIOLOGISTS LTD

Año: 2021 vol. 134

0021-9533

Cyclophilin A (CyPA, also known as PPIA) is an abundant andubiquitously expressed protein belonging to the immunophilin family,which has intrinsic peptidyl-prolyl-(cis/trans)-isomerase enzymaticactivity. CyPA mediates immunosuppressive action of the cyclicundecapeptide cyclosporine A and is also involved in multiple cellularprocesses, such as protein folding, intracellular trafficking, signaltransduction and transcriptional regulation. CyPA is abundantlyexpressed in cancer cells, and, owing to its chaperone nature, itsexpression is induced upon the onset of stress. In this study, wedemonstrated that a significant pool of this immunophilin is primarily anintramitochondrial factor that migrates to the nucleus when cells arestimulated with stressors. CyPA shows anti-apoptotic action per se andthe capability of forming ternary complexes with cytochrome c and thesmall acidic co-chaperone p23, the latter interaction being independentof the usual association of p23 with the heat-shock protein of 90 kDa,Hsp90. These CyPA?p23 complexes enhance the anti-apoptoticresponse of the cell, suggesting that both proteins form a functionalunit, the high level of expression of which plays a significant role in cellsurvival.