Peptidyl-prolyl cis-trans isomerase F, mitochondrial (Cyclophilin D) (CypD)

Cyclophilin D (CypD), encoded by the PPIF gene, is a peptidyl-prolyl cis-trans isomerase located within the mitochondrial matrix (UniProt P30405). It serves as a key regulatory component of the mitochondrial permeability transition pore (mPTP), a high-conductance channel in the inner mitochondrial membrane (PubMed: 15744310). Under physiological conditions, CypD helps maintain mitochondrial function, but during pathological stress—such as oxidative stress or calcium overload—it triggers the opening of the mPTP. This opening leads to mitochondrial swelling, loss of membrane potential, and the release of pro-apoptotic factors, ultimately resulting in cell death via necrosis or apoptosis (PubMed: 15744311). Consequently, CypD is a significant therapeutic target for diseases characterized by mitochondrial dysfunction, including myocardial ischemia-reperfusion injury, stroke, and neurodegenerative conditions like Alzheimer's and Parkinson's diseases (PubMed: 25648232). Drugs like Cyclosporine A and its non-immunosuppressive analogs, such as Alisporivir, target CypD to prevent mPTP opening and protect cells from injury (PubMed: 21854169).

Other names

PPIFCyclophilin FMitochondrial cyclophilinRotamase FCyclophilin 18Cyp-F

Inhibition of the peptidyl-prolyl isomerase activity of Cyclophilin D, which prevents its interaction with the mitochondrial permeability transition pore (mPTP) complex, thereby inhibiting pore opening and subsequent cell death (PubMed: 15744310).