Cyclophilins and their possible role in the stress response

Cyclophilins are proteins which are remarkably conserved through evolution; moreover they have been found in every possible existing organism, which i ndicates their fundamental importance. Due to their enzymatic properties, m ultiplicity, cellular localization and role in protein folding they belong to the group of proteins termed molecular chaperones. All the proteins of t he cyclophilin family possess enzymatic peptidyl-prolyl isomerase activity (PPl-ase), which is essential to protein folding in vivo. Recently PPl-ase activity was suggested as playing a role in regulation of transcription and differentiation, However, not all cyclophilin functions are explained by P PI-ase activity. For instance, one of the cyclophilins plays a regulatory r ole in the heat shock response and the mitochondrial cyclophilin (Cyclophil in D) is an integral part of the mitochondrial permeability transition comp lex, which is regarded as having a crucial role in mechanisms of cell death . In support of a role in the stress response, the expression of certain cy clophilins has recently been shown to be up-regulated under various stressf ul conditions. Current evidence of functional involvement of cyclophilins i n various intracellular pathways is reviewed along with the indications tha t cyclophilin D (Cyp D) represents a crucial part of the mitochondrial perm eability transition pore, which is detrimental in apoptotic and necrotic ce ll death. This review does not attempt to cover all the existing informatio n related to cyclophilin family of proteins, but focus on the existing evid ence of the involvement of these proteins in the intracellular stress respo nse.