Ask about this productRelated genes to: PPIF antibody
- Gene:
- PPIF NIH gene
- Name:
- peptidylprolyl isomerase F
- Previous symbol:
- -
- Synonyms:
- hCyP3, Cyp-D
- Chromosome:
- 10q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-06-02
- Date modifiied:
- 2015-09-07
Related products to: PPIF antibody
Related articles to: PPIF antibody
- Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD)-dependent mitochondrial deacetylase that regulates protein acetylation and maintains mitochondrial homeostasis in nucleated cells. By deacetylating cyclophilin D (CypD), SIRT3 limits mitochondrial permeability transition pore (mPTP) opening and protects against mitochondrial dysfunction. Although SIRT3 is present in murine and human platelets, its contribution to platelet mitochondrial regulation and procoagulant platelet formation remains unknown. This study investigated whether platelet SIRT3 modulates CypD-dependent procoagulant platelet formation. Platelets obtained from platelet-specific Sirt3 knockout mice () and littermate controls () were analyzed under resting conditions and after activation with CRP-XL and thrombin. Flow cytometry was used to analyze platelet (activation) markers and procoagulant platelet formation, and mitochondrial respiration was assessed using a Seahorse extracellular flux analyzer. Platelets lacking SIRT3 showed no alterations in basal or agonist-stimulated mitochondrial respiration. Likewise, platelet deletion did not affect the generation of procoagulant platelets in response to strong dual agonist stimulation. These findings indicate that, despite its role in regulating mPTP opening in nucleated cells, platelet SIRT3 is not required for procoagulant platelet formation, suggesting that platelets rely on distinct mechanisms for mPTP regulation. - Source: PubMed
Publication date: 2026/09/03
Van Bael JensDelmote Anne-SophiePareyn IngePirotton Laurencede Cartier d'Yves EmmaHorman SandrineSenis Yotis AAuwerx JohanDe Meyer Simon FVanhoorelbeke KarenTersteeg Claudia - Mechanical stimulation is fundamental for anabolism in various tissues, including bone. Importantly, mechanical stimulation has been shown to induce reprogramming of cell metabolism, likely to adjust it to increased anabolism. The signal transduction within this mechano-metabolic axis is incompletely understood. Aiming to delineate such signal transduction, we exposed osteoprogenitors to fluid shear stress (FSS) and assessed cell signaling and bioenergetics. The BMP/Smad pathway is known to be activated by mechanical stress, and we indeed detected its activation by FSS. We previously reported that BMP downregulates cyclophilin D (CypD), an opener of the mitochondrial permeability transition pore (MPTP). Downregulation of CypD/MPTP improves mitochondrial inner membrane integrity and therefore oxidative function. We found that in FSS-stimulated cells, CypD was indeed downregulated and mitochondria were activated in a BMP-dependent manner. Meanwhile, the osteogenic effect of FSS was dependent on CypD downregulation and mitochondrial responses. To confirm our in vitro results in vivo, we optimized a novel model of tooth extraction-mediated unloading of craniofacial bones in mice. Such unloading led to bone loss and upregulation of CypD in the affected bone. Osteoblast-specific deletion of CypD protected against unloading-mediated bone loss, while CypD re-expression in these mice restored bone loss. In sum, we here present new evidence that the mechano-metabolic axis in osteogenic cells involves BMP/Smad-mediated downregulation of CypD and CypD-dependent mitochondrial responses. Such regulation is important for the osteoanabolic effect of mechanical stimulation. Our data also suggest that targeting CypD can be an effective strategy to prevent bone loss caused by unloading due to immobility, space flight, or tooth extraction. - Source: PubMed
Publication date: 2026/09/02
Sautchuk RubensNieves Santana JosaranieYu ChenAwad HaniEliseev Roman A - The mitochondrial permeability transition pore (mPTP) opening is a phenomenon in which the inner mitochondrial membrane abruptly becomes permeable when matrix calcium reaches a critical threshold. Despite 5 decades of intensive research, no protein has been universally accepted as essential for mPTP opening, limiting mechanistic understanding and raising questions about the validity of mPTP-targeted strategies to mitigate cardiac ischemia-reperfusion (I/R) injury. Here, we discuss convergent findings from two independent laboratories identifying the innate immune receptor NLRX1 as an unexpected, essential requirement for mPTP activity. NLRX1 is the only NOD-like receptor (NLR) that is targeted to the mitochondrion. NLRX1 deficiency abolishes (1) calcium-induced mPTP opening, (2) cyclosporine A sensitivity of the pore, and (3) mitochondrial calcium release following cardiac I/R. To test whether loss of mPTP function aligns with loss of NLRX1 across evolution, we performed forward and reciprocal bioinformatic (Blastp) searches and found that species reported to lack an mPTP (e.g., Artemia franciscana and Drosophila melanogaster) also lack NLRX1, further supporting a mandatory role for NLRX1 in mPTP occurrence. Notably, NLRX1-deficient hearts can exhibit increased, rather than decreased, I/R injury at specific ischemia durations. This mirrors reports that deletion of established mPTP regulators (e.g., Ppif) may also worsen injury under defined conditions, consistent with context-dependent, potentially protective roles for transient mPTP activity (e.g., mitochondrial calcium release, PI3K/Akt signaling). In summary, we propose that NLRX1 is the only currently identified protein that is strictly required for mPTP opening, and that indiscriminate inhibition of the mPTP is unlikely to represent a universally effective cardioprotective strategy against I/R injury. - Source: PubMed
Publication date: 2026/08/19
Zuurbier Kielen RZuurbier Coert J - Ppif (Cyclophilin D, CypD) is a key regulator of mitochondrial permeability transition pore (mPTP) opening and plays an important role in maintaining mitochondrial homeostasis by regulating mitochondrial calcium dynamics and redox balance. Although Ppif deficiency has been reported to alter basal mitochondrial function, its impact on hepatocyte responses to carcinogenic stress and hepatocarcinogenesis remains poorly understood. Here, we investigated how Ppif deficiency influences acute cellular responses to diethylnitrosamine (DEN) and the subsequent development of liver tumors. Primary hepatocytes isolated from Ppif -knockout mice exhibited increased basal oxygen consumption and elevated mitochondrial and cellular ROS levels compared with wild-type hepatocytes. Following DEN challenge, Ppif-deficient hepatocytes showed enhanced ROS, increased DNA damage, and greater HIF1α accumulation. Despite these enhanced stress responses, caspase-3 activation and hepatocyte death were attenuated in Ppif-deficient hepatocytes, suggesting altered cellular adaptation to DEN-induced injury. Consistent with these acute responses, chronic DEN treatment resulted in increased oxidative DNA damage, elevated Ki67-positive proliferating cells, and significantly enhanced liver tumor burden in Ppif-deficient mice. Collectively, our findings demonstrate that Ppif deficiency alters hepatocyte responses to carcinogenic stress by promoting the survival of damaged hepatocytes, thereby facilitating DEN-induced hepatocarcinogenesis. These findings identify Ppif as a critical regulator of hepatocyte responses to carcinogenic stress during liver tumor development. - Source: PubMed
Publication date: 2026/07/22
Park Hye-KyungHu SungSong HanaKang Byoung HeonChoi Soo Youn - Mitochondrial dysfunction is considered a hallmark of the aging brain, and this organelle can be affected by several neurodegenerative conditions, leading to slowed bioenergetics and reduced energy production. These processes will affect neuronal communication and synaptic plasticity, generating cognitive decline during aging. Interestingly, we previously observed that mitochondrial dysfunction can be influenced by pathological forms of tau, which are posttranslational modifications of this protein implicated in neurodegeneration and aging. In this context, accumulating evidence indicates that mitochondrial impairment may be associated with activation of the mitochondrial permeability transition pore (mPTP). mPTP has been described as a critical regulator of mitochondrial function, and its pathological activation by cyclophilin D (CypD) induces neurodegeneration and reduces brain function. However, the role of CypD/mPTP on cognitive decline and its implications on tau pathology and neurodegeneration during aging has not been studied. Therefore, we evaluated the contribution of CypD/mPTP in mitochondrial dysfunction, cognitive decline, and tau pathology observed in aging animals. Aging mice lacking CypD expression (CypD-/-) (24-month-old) showed better cognitive performance, improved mitochondrial bioenergetics, increased ATP production, and mPTP closure compared with age-matched wild-type mice (24-month-old) with endogenous expression of CypD. Consequently, hippocampal tissue from aged wild-type animals showed a significant decrease in presynaptic protein levels (SV2) compared to aged CypD-/- animals. More importantly, CypD ablation prevented caspase-3 cleaved tau accumulation in the cytosolic and mitochondrial fractions of hippocampal tissue from 24-month-old mice, in contrast with wild-type aged mice that expressed endogenous CypD. These novel results indicate that CypD acts as a neurodegenerative promoter, inducing synaptic defects and cognitive decline by opening mPTP and mitochondrial dysfunction. More importantly, CypD contributes to the neurodegenerative effects of caspase-3-cleaved tau during aging, suggesting a novel neurodegenerative target induced by tau pathology. - Source: PubMed
Publication date: 2026/07/09
Olesen Margrethe AIsla EduardoJohnson Gail V WPorter George AQuintanilla Rodrigo A