PPIF
Description
The PPIF (peptidylprolyl isomerase F) is a protein-coding gene located on chromosome 10.
Peptidyl-prolyl cis-trans isomerase, mitochondrial (PPIF) is an enzyme that in humans is encoded by the PPIF gene. It has also been referred to as, but should not be confused with, cyclophilin D (CypD), which is encoded by the PPID gene. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to facilitate folding or repair of proteins. PPIF is a major component of the mitochondrial permeability transition pore (MPTP) and, thus, highly involved in mitochondrial metabolism and apoptosis, as well as in mitochondrial diseases and related conditions, including cardiac diseases, neurodegenerative diseases, and muscular dystrophy. In addition, PPIF participates in inflammation, as well as in ischemic reperfusion injury, AIDS, and cancer.
== Structure == Like other cyclophilins, PPIF forms a β-barrel structure with a hydrophobic core. This β-barrel is composed of eight anti-parallel β-strands and capped by two α-helices at the top and bottom. In addition, the β-turns and loops in the strands contribute to the flexibility of the barrel. PPIF weighs 17.5 kDa and forms part of the MPTP in the inner mitochondrial membrane (IMM).
== Function == The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family.
PPIF, also known as Cyclophilin D, catalyzes the conversion of proline peptide bonds between cis and trans conformations, potentially assisting protein folding. PPIF regulates the mitochondrial permeability transition pore (mPTP), potentially masking a binding site for inhibiting inorganic phosphate (Pi) and promoting the opening of the mPTP, which can lead to apoptosis or necrosis. Its role in this process may require its PPIase activity. PPIF cooperates with mitochondrial p53 to activate necrosis in response to oxidative stress. PPIF also modulates mitochondrial F(1)F(0) ATP synthase activity, regulating adenine nucleotide levels within the mitochondria. Notably, PPIF exhibits anti-apoptotic activity independent of the mPTP and works with BCL2 to inhibit cytochrome c-dependent apoptosis. PPIF interacts with ATP5F1B, ATP5PD, ATP5PO, SLC25A3, BCL2, TP53, C1QBP, and MCUR1. This interaction with SLC25A3 is impeded by CsA. Similarly, the association with BCL2 and TP53 is blocked by CsA. The interaction with TP53 favors tetrameric TP53 and is triggered by oxidative stress. PPIF forms part of the mitochondrial permeability transition pore complex (mPTPC), along with SPG7 and VDAC1. It interacts with SPG7.
PPIF is also known as CYP3, CyP-M, Cyp-D, CypD.
