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

Cyclophilin F, also known as Peptidyl-prolyl cis-trans isomerase F (PPIF) or mitochondrial Cyclophilin D, is a member of the immunophilin family located in the mitochondrial matrix [1, 13]. It functions as a peptidyl-prolyl cis-trans isomerase (PPIase), facilitating protein folding by catalyzing the isomerization of proline imidic peptide bonds [3, 13]. Its most critical role is the regulation of the mitochondrial permeability transition pore (mPTP), where it acts as a modulatory component that promotes pore opening in response to calcium overload or oxidative stress [1, 16]. The opening of the mPTP leads to mitochondrial swelling, loss of membrane potential, and subsequent cell death via necrosis or apoptosis [2, 4]. Because of this role, Cyclophilin F is a major therapeutic target for conditions involving mitochondrial dysfunction, such as ischemia-reperfusion injury in the heart and kidneys, and neurodegenerative diseases like Alzheimer's and Parkinson's [3, 6, 9]. It is also implicated in the pathogenesis of muscular dystrophies and traumatic brain injury [3, 6]. Drugs such as Cyclosporine A and its non-immunosuppressive derivatives, like Alisporivir, target Cyclophilin F to inhibit its isomerase activity and prevent mPTP opening [1, 9, 11]. Therapeutic challenges include achieving isoform specificity to avoid off-target effects on other cyclophilins and managing the potential for immunosuppression when using certain inhibitors [7, 9].

Other names

Cyclophilin FCyclophilin DCypDCypFMitochondrial cyclophilinPPIase FRotamase FCYP3

Inhibition of peptidyl-prolyl cis-trans isomerase activity and prevention of mitochondrial permeability transition pore (mPTP) opening.