Cyclophilin-F, also known as Peptidyl-prolyl cis-trans isomerase F (PPIF), is a member of the cyclophilin family of peptidyl-prolyl isomerases. These enzymes catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides, which is a crucial process in protein folding and function. Cyclophilin-F is particularly notable for its role in mitochondrial function and its involvement in the regulation of the mitochondrial permeability transition pore (mPTP).
Cyclophilin-F is a protein that is encoded by the PPIF gene in humans. It is expressed in various tissues and is predominantly localized in the mitochondria. The protein has a molecular weight of approximately 17.8 kDa . Cyclophilin-F exhibits peptidyl-prolyl isomerase activity, which facilitates the proper folding of proteins by catalyzing the cis-trans isomerization of proline residues.
One of the key functions of Cyclophilin-F is its regulation of the mPTP, a multi-protein complex that controls the permeability of the mitochondrial membrane. The opening of the mPTP can lead to the loss of mitochondrial membrane potential, release of pro-apoptotic factors, and ultimately cell death. Cyclophilin-F interacts with other components of the mPTP, such as adenine nucleotide translocase (ANT) and voltage-dependent anion channel (VDAC), to modulate its opening and closing .
Cyclophilin-F has been implicated in various pathological conditions, particularly those involving mitochondrial dysfunction. Its role in the regulation of the mPTP makes it a critical player in processes such as apoptosis and necrosis. Dysregulation of Cyclophilin-F activity has been associated with several diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer .
For instance, in the context of neurodegenerative diseases, the excessive opening of the mPTP can lead to neuronal cell death, contributing to conditions such as Alzheimer’s disease and Parkinson’s disease. In cardiovascular diseases, Cyclophilin-F-mediated mPTP opening can result in cardiomyocyte death, which is a key event in ischemia-reperfusion injury .
Given its central role in mitochondrial function and cell death, Cyclophilin-F is considered a potential therapeutic target for various diseases. Inhibitors of Cyclophilin-F, such as cyclosporin A, have been shown to prevent the opening of the mPTP and protect against cell death in experimental models. These findings suggest that targeting Cyclophilin-F could be a viable strategy for treating diseases associated with mitochondrial dysfunction .
Human recombinant Cyclophilin-F is produced using recombinant DNA technology, typically expressed in Escherichia coli (E. coli) systems. This recombinant protein is used in research to study its structure, function, and interactions with other proteins. It is also employed in drug discovery efforts to identify and characterize potential inhibitors of Cyclophilin-F .