Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF) is a 207-amino acid protein that catalyzes the cis-trans isomerization of proline peptide bonds, assisting protein folding and participating in mitochondrial quality control (UniProt: P30405). It plays a central regulatory role in the mitochondrial permeability transition pore (mPTP), modulating its open probability and influencing cell death pathways. PPIF also cooperates with p53 in oxidative stress-induced necrosis and possesses anti-apoptotic activity independent of mPTP function, inhibiting cytochrome c-dependent apoptosis in cooperation with BCL2 (UniProt: P30405).

In Alzheimer's Disease, PPIF is upregulated in post-mortem human brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomic analysis using TMT labeling across four subcellular fractions detected a mean log2 fold-change of 0.44, indicating modest but consistent upregulation. This elevation suggests enhanced mitochondrial stress response or perturbation of mPTP regulation in AD pathology, potentially contributing to the bioenergetic and apoptotic dysfunctions characteristic of neurodegeneration.