Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF)

Peptidyl-prolyl cis-trans isomerase F, mitochondrial (commonly called Cyclophilin D, encoded by the gene PPIF), is a mitochondrial matrix enzyme of the cyclophilin family that catalyzes the cis-trans isomerization of proline imidic peptide bonds and thereby assists in mitochondrial protein folding[1][2][7]. Cyclophilin D plays a key regulatory role in opening the mitochondrial permeability transition pore (mPTP), a critical event in cell death pathways, especially during stress conditions like ischemia/reperfusion and neurodegenerative diseases[2][5][8]. Pharmacologic and genetic inhibition of Cyclophilin D (notably by cyclosporin A) has protective effects against pathological cell death by stabilizing mitochondrial membrane integrity, making it a validated but challenging therapeutic target for conditions marked by mitochondrial dysfunction, oxidative stress, or aberrant cell survival such as neurodegeneration, cardiovascular events, muscular dystrophy, and cellular senescence[1][2][5][8]. Cyclophilin D’s essential functions in normal cell biology impose therapeutic challenges, particularly with respect to toxicity and specificity[3][5].

Other names

Cyclophilin DCypDCyP-DCyclophilin FCyp-MPPIase FPPIFmitochondrial cyclophilinRotamase FCYP3peptidylprolyl isomerase F

Inhibition of PPIF (Cyclophilin D) leads to blockade of mPTP opening, reducing cell death in stress conditions such as ischemia/reperfusion[1][2][5][8]. Cyclosporin A binds to Cyclophilin D, inhibiting its function and modulating mitochondrial permeability and cell fate[2][5].