Gene Symbol: Ppid
Description: peptidylprolyl isomerase D (cyclophilin D)
Alias: 4930564J03Rik, CYP-40, Ppidl, Ppif, peptidyl-prolyl cis-trans isomerase D, 40 kDa peptidyl-prolyl cis-trans isomerase, PPIase D, cyclophilin-40, cytoplasmic cyclophilin D, rotamase D
Species: mouse
Products:     Ppid

Top Publications

  1. Schinzel A, Takeuchi O, Huang Z, Fisher J, Zhou Z, Rubens J, et al. Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci U S A. 2005;102:12005-10 pubmed
  2. Naga K, Sullivan P, Geddes J. High cyclophilin D content of synaptic mitochondria results in increased vulnerability to permeability transition. J Neurosci. 2007;27:7469-75 pubmed
    ..in Ca2+ handling between synaptic and nonsynaptic mitochondria were greatly reduced in cyclophilin D null [Ppif-/- (peptidylprolyl isomerase F)] mice...
  3. Zamorano S, Rojas Rivera D, Lisbona F, Parra V, Court F, Villegas R, et al. A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway. PLoS ONE. 2012;7:e37782 pubmed publisher
    ..Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria. ..
  4. Whelan R, Konstantinidis K, Wei A, Chen Y, Reyna D, Jha S, et al. Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A. 2012;109:6566-71 pubmed publisher
    ..Thus, Bax and Bak play wider roles in cell death than previously appreciated and may be optimal therapeutic targets for diseases that involve both forms of cell death. ..
  5. Forte M, Gold B, Marracci G, Chaudhary P, Basso E, Johnsen D, et al. Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc Natl Acad Sci U S A. 2007;104:7558-63 pubmed
    ..Our results directly implicate pathological activation of the mitochondrial PTP in the axonal damage occurring during MS and identify CyPD, as well as the PTP, as a potential target for MS neuroprotective therapies. ..
  6. Ramachandran A, Lebofsky M, Baines C, Lemasters J, Jaeschke H. Cyclophilin D deficiency protects against acetaminophen-induced oxidant stress and liver injury. Free Radic Res. 2011;45:156-64 pubmed publisher
    ..CypD-deficient (Ppif(-/-)) mice were completely protected against APAP-induced liver injury and DNA fragmentation...
  7. Palma E, Tiepolo T, Angelin A, Sabatelli P, Maraldi N, Basso E, et al. Genetic ablation of cyclophilin D rescues mitochondrial defects and prevents muscle apoptosis in collagen VI myopathic mice. Hum Mol Genet. 2009;18:2024-31 pubmed publisher
  8. Li V, Brustovetsky T, Brustovetsky N. Role of cyclophilin D-dependent mitochondrial permeability transition in glutamate-induced calcium deregulation and excitotoxic neuronal death. Exp Neurol. 2009;218:171-82 pubmed publisher
    ..We used cultured cortical neurons from wild-type C57BL/6 and cyclophilin D-knockout mice (Ppif(-/-))...
  9. Basso E, Fante L, Fowlkes J, Petronilli V, Forte M, Bernardi P. Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D. J Biol Chem. 2005;280:18558-61 pubmed
    ..studied the properties of the permeability transition pore (PTP) in mitochondria from the liver of mice where the Ppif gene encoding for mitochondrial Cyclophilin D (CyP-D) had been inactivated...

More Information


  1. Park J, Pasupulati R, Feldkamp T, Roeser N, Weinberg J. Cyclophilin D and the mitochondrial permeability transition in kidney proximal tubules after hypoxic and ischemic injury. Am J Physiol Renal Physiol. 2011;301:F134-50 pubmed publisher
    ..and hypoxia-reoxygenation (H/R), we assessed freshly isolated tubules and in vivo injury in wild-type (WT) and Ppif(-/-) CyPD-null mice...
  2. Perier C, Bove J, Wu D, Dehay B, Choi D, Jackson Lewis V, et al. Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease. Proc Natl Acad Sci U S A. 2007;104:8161-6 pubmed
    ..These results provide further insight into the pathogenesis of PD neurodegeneration and identify molecular targets of potential therapeutic significance for this disabling neurological illness. ..
  3. Baines C, Kaiser R, Sheiko T, Craigen W, Molkentin J. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol. 2007;9:550-5 pubmed
    ..These results indicate that Vdacs are dispensable for both MPT and Bcl-2 family member-driven cell death. ..
  4. Yokoi H, Shimizu Y, Anazawa H, Lefebvre C, Korneluk R, Ikeda J. The structure and complete nucleotide sequence of the human cyclophilin 40 (PPID) gene. Genomics. 1996;35:448-55 pubmed
    b>Cyclophilin 40 is a recently identified member of the cyclophilin family that is found in an unactivated steroid hormone receptor complex...
  5. Nakayama H, Chen X, Baines C, Klevitsky R, Zhang X, Zhang H, et al. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest. 2007;117:2431-44 pubmed
  6. Kim S, Shim M, Kim K, Weinreb R, Wheeler L, Ju W. Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury. Cell Death Dis. 2014;5:e1105 pubmed publisher
    ..On the basis of these observations, our findings suggest that CsA-mediated CypD inhibition may provide a promising therapeutic potential for protecting RGCs against ischemic injury-mediated mitochondrial dysfunction. ..
  7. Menazza S, Wong R, Nguyen T, Wang G, Gucek M, Murphy E. CypD(-/-) hearts have altered levels of proteins involved in Krebs cycle, branch chain amino acid degradation and pyruvate metabolism. J Mol Cell Cardiol. 2013;56:81-90 pubmed publisher
    ..In summary, CypD(-/-) hearts exhibit changes in many metabolic pathways and caution should be used when interpreting results from these mice as due solely to inhibition of the MPTP. ..
  8. Jobe S, Wilson K, Leo L, Raimondi A, Molkentin J, Lentz S, et al. Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis. Blood. 2008;111:1257-65 pubmed
    ..These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis. ..
  9. Harisseh R, Chiari P, Villedieu C, Sueur P, Abrial M, Fellahi J, et al. Cyclophilin D Modulates the Cardiac Mitochondrial Target of Isoflurane, Sevoflurane, and Desflurane. J Cardiovasc Pharmacol. 2017;69:326-334 pubmed publisher
  10. Zhu X, Hogan S, Molkentin J, Zimmermann N. Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils. Am J Physiol Gastrointest Liver Physiol. 2016;310:G609-17 pubmed publisher
    ..Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and ..
  11. Shang W, Gao H, Lu F, Ma Q, Fang H, Sun T, et al. Cyclophilin D regulates mitochondrial flashes and metabolism in cardiac myocytes. J Mol Cell Cardiol. 2016;91:63-71 pubmed publisher
    ..In addition, tissue-specific CyP-D expression may partly explain the differential regulation of mitoflashes in the two types of striated muscles. ..
  12. Tavecchio M, Lisanti S, Lam A, Ghosh J, Martin N, O CONNELL M, et al. Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility. J Biol Chem. 2013;288:5553-61 pubmed publisher
    ..Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation ..
  13. Ideguchi K, Shimizu S, Okumura M, Tsujimoto Y. Cyclophilin D-dependent mitochondrial permeability transition is not involved in neurodegeneration in mnd2 mutant mice. Biochem Biophys Res Commun. 2010;393:264-7 pubmed publisher
    ..Our data suggest that CypD-dependent mPT does not play a major role in neurodegeneration in mnd2 mice. ..
  14. Doczi J, Turiak L, Vajda S, Mandi M, Torocsik B, Gerencser A, et al. Complex contribution of cyclophilin D to Ca2+-induced permeability transition in brain mitochondria, with relation to the bioenergetic state. J Biol Chem. 2011;286:6345-53 pubmed publisher
    ..These findings could explain why absence of cypD protects against necrotic (deenergized mitochondria), but not apoptotic (energized mitochondria) stimuli. ..
  15. Reyes R, Perry G, Lesort M, Parpura V. Immunophilin deficiency augments Ca2+-dependent glutamate release from mouse cortical astrocytes. Cell Calcium. 2011;49:23-34 pubmed publisher
    ..Cortical astrocytes isolated from CypD deficient mice Ppif(-/-) displayed reduced mechanically induced Ca(cyt)(2+) increases, even though these cells showed augmented ..
  16. Millay D, Sargent M, Osinska H, Baines C, Barton E, Vuagniaux G, et al. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat Med. 2008;14:442-7 pubmed publisher
    ..Here we show that deletion of the gene encoding cyclophilin D (Ppif) rendered mitochondria largely insensitive to the calcium overload-induced swelling associated with a defective ..
  17. Schneider M. Cyclophilin D: knocking on death's door. Sci STKE. 2005;2005:pe26 pubmed
    ..These data raise questions about the relationship between apoptotic and necrotic cell death, and they also highlight cyclophilin D as a potential therapeutic target in myocardial infarction. ..
  18. Bourke C, Raees M, Malviya S, Bradburn C, Binder E, Neigh G. Glucocorticoid sensitizers Bag1 and Ppid are regulated by adolescent stress in a sex-dependent manner. Psychoneuroendocrinology. 2013;38:84-93 pubmed publisher
    ..Gene expression of Ppid, a positive regulator of the GR, was predicted by plasma estradiol and 34% lower in control adolescent females than ..
  19. Nguyen T, Stevens M, KOHR M, Steenbergen C, Sack M, Murphy E. Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore. J Biol Chem. 2011;286:40184-92 pubmed publisher
    ..Our results indicate that the Cys-203 residue of CypD is necessary for redox stress-induced activation of mPTP. ..
  20. Vaseva A, Marchenko N, Ji K, Tsirka S, Holzmann S, Moll U. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012;149:1536-48 pubmed publisher
    ..Our study identifies the mitochondrial p53-CypD axis as an important contributor to oxidative stress-induced necrosis and implicates this axis in stroke pathology. ..
  21. Daussin F, Godin R, Ascah A, DeschĂȘnes S, Burelle Y. Cyclophilin-D is dispensable for atrophy and mitochondrial apoptotic signalling in denervated muscle. J Physiol. 2011;589:855-61 pubmed publisher
    ..Altogether, these results provide direct evidence that CypD-dependent PTP opening is dispensable for atrophy and apoptotic signalling in skeletal muscle following denervation. ..
  22. Giorgio V, Bisetto E, Soriano M, Dabbeni Sala F, Basso E, Petronilli V, et al. Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting with the lateral stalk of the complex. J Biol Chem. 2009;284:33982-8 pubmed publisher
    ..These findings demonstrate that CyPD association to the lateral stalk of ATP synthase modulates the activity of the complex. ..