Gene Symbol: Ppif
Description: peptidylprolyl isomerase F
Alias: CyP-D, CypD, PPIase, peptidyl-prolyl cis-trans isomerase F, mitochondrial, PPIase F, cyclophilin D, cyclophilin F, rotamase F
Species: rat
Products:     Ppif

Top Publications

  1. Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, et al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature. 2005;434:652-8 pubmed
    ..We therefore created mice lacking cyclophilin D (CypD), a protein considered to be involved in the mPT, to analyse its role in cell death...
  2. Machida K, Ohta Y, Osada H. Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells. J Biol Chem. 2006;281:14314-20 pubmed
    The permeability transition pore is involved in the mitochondrial pathway of apoptosis. Cyclophilin D, a pore component, has catalytic activity as a peptidyl prolyl cis, trans-isomerase (PPIase), which is essential to the pore opening...
  3. Baines C, Kaiser R, Purcell N, Blair N, Osinska H, Hambleton M, et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005;434:658-62 pubmed
    ..mPT pore is thought to consist of the adenine nucleotide translocator, a voltage-dependent anion channel, and cyclophilin D (the Ppif gene product), a prolyl isomerase located within the mitochondrial matrix...
  4. 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
    ..Consequently, PT has been implicated in both apoptotic and necrotic cell death. Cyclophilin D (CypD) appears to be a critical component of the PTP...
  5. Leung A, Varanyuwatana P, Halestrap A. The mitochondrial phosphate carrier interacts with cyclophilin D and may play a key role in the permeability transition. J Biol Chem. 2008;283:26312-23 pubmed publisher
    ..An interaction of the PiC with the ANT may enable agents that bind to either transporter to modulate pore opening...
  6. Li Y, Johnson N, Capano M, Edwards M, Crompton M. Cyclophilin-D promotes the mitochondrial permeability transition but has opposite effects on apoptosis and necrosis. Biochem J. 2004;383:101-9 pubmed
    ..These findings indicate that the permeability transition leads to cell necrosis, but argue against its involvement in apoptosis. ..
  7. Csukly K, Ascah A, Matas J, Gardiner P, Fontaine E, Burelle Y. Muscle denervation promotes opening of the permeability transition pore and increases the expression of cyclophilin D. J Physiol. 2006;574:319-27 pubmed
    ..Cyclosporin A, which inhibits PTP opening by binding to cyclophilin D (CypD), was significantly more potent in mitochondria from denervated muscle and restored CRC to the level ..
  8. Kato M, Akao M, Matsumoto Ida M, Makiyama T, Iguchi M, Takeda T, et al. The targeting of cyclophilin D by RNAi as a novel cardioprotective therapy: evidence from two-photon imaging. Cardiovasc Res. 2009;83:335-44 pubmed publisher
    ..We aimed to investigate the protective effects of RNA interference (RNAi)-mediated gene silencing of cyclophilin D (CypD), one of the putative components of the MPTP, against myocardial ischaemia/reperfusion using two-photon ..
  9. Eliseev R, Malecki J, Lester T, Zhang Y, Humphrey J, Gunter T. Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect. J Biol Chem. 2009;284:9692-9 pubmed publisher
    b>Cyclophilin D (CypD) is a mitochondrial immunophilin and a key positive regulator of the mitochondrial permeability transition (MPT)...

More Information


  1. 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
    ..permeability transition pore (PTP) opening and necrosis by physical interaction with the PTP regulator cyclophilin D (CypD). Intriguingly, a robust p53-CypD complex forms during brain ischemia/reperfusion injury...
  2. Chiara F, Castellaro D, Marin O, Petronilli V, BRUSILOW W, Juhaszova M, et al. Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltage-dependent anion channels. PLoS ONE. 2008;3:e1852 pubmed publisher
    ..by inhibiting two established permeability transition pore modulators, the adenine nucleotide translocator or cyclophilin D, or in cyclophilin D knock-out cells...
  3. Malouitre S, Dube H, Selwood D, Crompton M. Mitochondrial targeting of cyclosporin A enables selective inhibition of cyclophilin-D and enhanced cytoprotection after glucose and oxygen deprivation. Biochem J. 2009;425:137-48 pubmed publisher
    ..Moreover, the therapeutic potential of CsA against ischaemia/reperfusion injuries not involving glutamate may be improved by mitochondrial targeting. ..
  4. Carreira R, Lee Y, Ghochani M, Gustafsson A, Gottlieb R. Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells. Autophagy. 2010;6:462-72 pubmed publisher
    ..Starvation failed to induce autophagy in CypD-deficient murine cardiomyocytes, whereas in myocytes from mice overexpressing CypD the levels of autophagy were ..
  5. Hu W, Chen Z, Ye Z, Xia D, Xia Z, Ma J, et al. Knockdown of Cyclophilin D Gene by RNAi Protects Rat from Ischemia/ Reperfusion-Induced Renal Injury. Kidney Blood Press Res. 2010;33:193-9 pubmed publisher
    ..a channel which putatively consists of a voltage-dependent anion channel, adenine nucleotide translocator and cyclophilin D (CypD). Much evidence shows that CypD plays an important role in I/R-induced injury...
  6. Shanmughapriya S, Rajan S, Hoffman N, Higgins A, Tomar D, Nemani N, et al. SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore. Mol Cell. 2015;60:47-62 pubmed publisher
    ..Loss of SPG7 resulted in higher mitochondrial Ca(2+) retention, similar to cyclophilin D (CypD, PPIF) knockdown with sustained ΔΨm during both Ca(2+) and ROS stress...
  7. Connern C, Halestrap A. Purification and N-terminal sequencing of peptidyl-prolyl cis-trans-isomerase from rat liver mitochondrial matrix reveals the existence of a distinct mitochondrial cyclophilin. Biochem J. 1992;284 ( Pt 2):381-5 pubmed
    1. Rat liver mitochondrial matrix peptidyl-prolyl cis-trans-isomerase (PPIase) has been purified. The major form of the enzyme has a molecular mass of 18.6 kDa, with a minor active component of 17.6 kDa. 2...
  8. Chinopoulos C, Konràd C, Kiss G, Metelkin E, Torocsik B, Zhang S, et al. Modulation of F0F1-ATP synthase activity by cyclophilin D regulates matrix adenine nucleotide levels. FEBS J. 2011;278:1112-25 pubmed publisher
    b>Cyclophilin D was recently shown to bind to and decrease the activity of F(0)F(1)-ATP synthase in submitochondrial particles and permeabilized mitochondria [Giorgio V et al. (2009) J Biol Chem, 284, 33982-33988]...
  9. Woodfield K, Ruck A, Brdiczka D, Halestrap A. Direct demonstration of a specific interaction between cyclophilin-D and the adenine nucleotide translocase confirms their role in the mitochondrial permeability transition. Biochem J. 1998;336 ( Pt 2):287-90 pubmed
    ..Binding was prevented by pretreatment of the CyP-D with CsA, but not with cyclosporin H. Purified ANT also bound specifically to GST-CyP-D, but porin did not, even in the presence of ANT. ..
  10. 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
    ..with the membrane-permeable bifunctional reagent dimethyl 3,3-dithiobis-propionimidate (DTBP) cross-linked CyPD with the lateral stalk of ATP synthase, whereas no interactions with F(1) sector subunits, the ATP synthase natural ..
  11. Matas J, Young N, Bourcier Lucas C, Ascah A, Marcil M, Deschepper C, et al. Increased expression and intramitochondrial translocation of cyclophilin-D associates with increased vulnerability of the permeability transition pore to stress-induced opening during compensated ventricular hypertrophy. J Mol Cell Cardiol. 2009;46:420-30 pubmed publisher
    ..of cyclophilin-D to mitochondrial membranes in a dose-related fashion, except when cyclosporin A (a ligand of cyclophilin D with a known ability to delay PTP opening) was present prior to the addition of terbutylhydroperoxyde...
  12. Hazelton J, Petrasheuskaya M, Fiskum G, Kristian T. Cyclophilin D is expressed predominantly in mitochondria of gamma-aminobutyric acidergic interneurons. J Neurosci Res. 2009;87:1250-9 pubmed publisher
    ..The cause for this heterogeneity is not clear, so we studied the distribution of a key regulator of the MPT, cyclophilin D (cypD), within the rat brain by using immunohistology and Western blotting...
  13. Eliseev R, Filippov G, Velos J, Vanwinkle B, Goldman A, Rosier R, et al. Role of cyclophilin D in the resistance of brain mitochondria to the permeability transition. Neurobiol Aging. 2007;28:1532-42 pubmed
    The mitochondrial permeability transition (MPT) is involved in both necrosis and apoptosis. Cyclophilin D (CypD) is an important component of the MPT...
  14. Lin D, Lechleiter J. Mitochondrial targeted cyclophilin D protects cells from cell death by peptidyl prolyl isomerization. J Biol Chem. 2002;277:31134-41 pubmed
    b>Cyclophilin D (CyPD) is thought to sensitize opening of the mitochondrial permeability transition pore (mPTP) based on the findings that cyclosporin A (CsA), a pseudo-CyPD substrate, hyperpolarizes the mitochondrial membrane potential (..
  15. Basso E, Petronilli V, Forte M, Bernardi P. Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation. J Biol Chem. 2008;283:26307-11 pubmed publisher
    ..was specifically required for PTP desensitization by cyclosporin A (CsA) or by genetic inactivation of cyclophilin D (CyP-D)...