Gene Symbol: Ppif
Description: peptidylprolyl isomerase F (cyclophilin F)
Alias: AW457192, CyP-D, CyP-F, CypD, PPIase, peptidyl-prolyl cis-trans isomerase F, mitochondrial, PPIase F, cyclophilin D, cyclophilin F, mitochondrial Cyclophilin D, peptidyl-prolyl cis-trans isomerase, mitochondrial, rotamase F
Species: mouse
Products:     Ppif

Top Publications

  1. 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
    ..transition pore (PTP) in mitochondria from the liver of mice where the Ppif gene encoding for mitochondrial Cyclophilin D (CyP-D) had been inactivated...
  2. 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...
  3. 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...
  4. He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009;137:1100-11 pubmed publisher
    ..These data indicate RIP3 as the determinant for cellular necrosis in response to TNF-alpha family of death-inducing cytokines. ..
  5. Elrod J, Wong R, Mishra S, Vagnozzi R, Sakthievel B, Goonasekera S, et al. Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest. 2010;120:3680-7 pubmed publisher
    b>Cyclophilin D (which is encoded by the Ppif gene) is a mitochondrial matrix peptidyl-prolyl isomerase known to modulate opening of the mitochondrial permeability transition pore (MPTP)...
  6. 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. ..
  7. 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...
  8. Du H, Guo L, Fang F, Chen D, Sosunov A, McKhann G, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med. 2008;14:1097-105 pubmed publisher
    b>Cyclophilin D (CypD, encoded by Ppif) is an integral part of the mitochondrial permeability transition pore, whose opening leads to cell death...
  9. 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
    ..In a murine disease model, experimental autoimmune encephalomyelitis (EAE) mice lacking cyclophilin D (CyPD), a key regulator of the mitochondrial permeability transition pore (PTP), developed EAE, but unlike WT ..

More Information


  1. Du H, Guo L, Zhang W, Rydzewska M, Yan S. Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging. 2011;32:398-406 pubmed publisher
    ..Mitochondrial A? has been linked to mitochondrial toxicity. Our recent study demonstrated that cyclophilin D (CypD) mediated mitochondrial permeability transition pore (mPTP) is an important mechanism for neuronal and ..
  2. Meier J, Hyun M, Cantwell M, Raza A, Mertens C, Raje V, et al. Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduce mitochondrial ROS production. Sci Signal. 2017;10: pubmed publisher
    ..Under these conditions, mitochondrially localized STAT3 also became competent to bind to cyclophilin D (CypD)...
  3. Martin L, Semenkow S, Hanaford A, Wong M. Mitochondrial permeability transition pore regulates Parkinson's disease development in mutant ?-synuclein transgenic mice. Neurobiol Aging. 2014;35:1132-52 pubmed publisher
    ..Genetic ablation of cyclophilin D, an mPTP modulator, delayed disease onset, and extended lifespans of mutant ?Syn mice...
  4. 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 previous studies have shown that cysteine 203 of cyclophilin D (CypD), a critical mPTP mediator, undergoes protein S-nitrosylation (SNO)...
  5. Bigi A, Beltrami E, Trinei M, Stendardo M, Pelicci P, Giorgio M. Cyclophilin D counteracts P53-mediated growth arrest and promotes Ras tumorigenesis. Oncogene. 2016;35:5132-43 pubmed publisher
    ..The mitochondrial pepdidyl-prolyl isomerase cyclophilin D (CypD) is an important regulator of the mitochondrial permeability transition and a key player in mitochondria ..
  6. Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, et al. Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A. 2013;110:5887-92 pubmed publisher
    ..The PTP is regulated by matrix cyclophilin D (CyPD), which also binds the lateral stalk of the FOF1 ATP synthase...
  7. Song M, Chen Y, Gong G, Murphy E, Rabinovitch P, Dorn G. Super-suppression of mitochondrial reactive oxygen species signaling impairs compensatory autophagy in primary mitophagic cardiomyopathy. Circ Res. 2014;115:348-53 pubmed publisher
    ..A therapeutic window for mitochondrial ROS suppression should minimize the former while retaining the latter, which we achieved by expressing lower levels of catalase. ..
  8. Wang K, An T, Zhou L, Liu C, Zhang X, Feng C, et al. E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death. Cell Death Differ. 2015;22:743-54 pubmed publisher
    ..Here we report that miR-30b, Cyclophilin D (CypD) and E2F1 constitute an axis that regulates necrosis...
  9. 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
    ..Triple knockout mice lacking Bax/Bak and cyclophilin D, a key regulator of necrosis, fail to show further reduction in infarct size over those deficient in Bax/Bak...
  10. Fujimoto K, Chen Y, Polonsky K, Dorn G. Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency. Proc Natl Acad Sci U S A. 2010;107:10214-9 pubmed publisher
    ..Preventing mitochondrial permeability transition pore opening with the cyclophilin D inhibitor cyclosporin A restored Deltapsi(m) and rescued cell viability...
  11. Su K, Savino C, Marracci G, Chaudhary P, Yu X, Morris B, et al. Genetic inactivation of the p66 isoform of ShcA is neuroprotective in a murine model of multiple sclerosis. Eur J Neurosci. 2012;35:562-71 pubmed publisher
    ..These results confirm the critical role of ROS-mediated mitochondrial dysfunction in the axonal loss that accompanies EAE, and identify p66 as a new pharmacologic target for MS neuroprotective therapeutics...
  12. 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
    In the present study we tested the hypothesis that the cyclophilin D-dependent (CyD) mitochondrial permeability transition (CyD-mPT) plays an important role in glutamate-triggered delayed calcium deregulation (DCD) and excitotoxic ..
  13. Beck S, Guo L, Phensy A, Tian J, Wang L, Tandon N, et al. Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer's disease. Nat Commun. 2016;7:11483 pubmed publisher
    ..Therefore, mitochondrial F1FO-ATP synthase dysfunction associated with AD progression could potentially be prevented by OSCP stabilization. ..
  14. Perry G, Tallaksen Greene S, Kumar A, Heng M, Kneynsberg A, van Groen T, et al. Mitochondrial calcium uptake capacity as a therapeutic target in the R6/2 mouse model of Huntington's disease. Hum Mol Genet. 2010;19:3354-71 pubmed publisher
    ..Mouse models lacking cyclophilin D demonstrate convincingly that cyclophilin D is an essential component and a key regulator of MPT induction...
  15. 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...
  16. Barsukova A, Komarov A, Hajnoczky G, Bernardi P, Bourdette D, Forte M. Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons. Eur J Neurosci. 2011;33:831-42 pubmed publisher
    ..evaluated neuronal Ca(2+) dynamics and the PTP in single adult neurons in wild-type mice and those missing cyclophilin D (CyPD), a key regulator of the PTP...
  17. Barsukova A, Bourdette D, Forte M. Mitochondrial calcium and its regulation in neurodegeneration induced by oxidative stress. Eur J Neurosci. 2011;34:437-47 pubmed publisher
    ..Elimination of cyclophilin D (CyPD), a key regulator of the PTP, results in neuroprotection in a number of murine models of ..
  18. Kerur N, Fukuda S, Banerjee D, Kim Y, Fu D, Apicella I, et al. cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nat Med. 2018;24:50-61 pubmed publisher
  19. Devalaraja Narashimha K, Diener A, Padanilam B. Cyclophilin D deficiency prevents diet-induced obesity in mice. FEBS Lett. 2011;585:677-82 pubmed publisher
    ..Here we show that deletion of cyclophilin D (CypD), a key modulator of the mitochondrial permeability transition pore, demonstrated resistance to diet-..
  20. 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]...
  21. Hausenloy D, Lim S, Ong S, Davidson S, Yellon D. Mitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning. Cardiovasc Res. 2010;88:67-74 pubmed publisher
    ..The aim of the present study is to determine whether the cyclophilin-D (CYPD) component of the mPTP is required by IPC to generate mitochondrial ROS and subsequently activate Akt and Erk1/2...
  22. Karch J, Kanisicak O, Brody M, Sargent M, Michael D, Molkentin J. Necroptosis Interfaces with MOMP and the MPTP in Mediating Cell Death. PLoS ONE. 2015;10:e0130520 pubmed publisher
    ..Here, we show cells or mice deficient for Bax/Bak or cyclophilin D, a protein that regulates MPTP opening, are resistant to cell death induced by necroptotic mediators...
  23. Bochaton T, Crola da Silva C, Pillot B, Villedieu C, Ferreras L, Alam M, et al. Inhibition of myocardial reperfusion injury by ischemic postconditioning requires sirtuin 3-mediated deacetylation of cyclophilin D. J Mol Cell Cardiol. 2015;84:61-9 pubmed publisher
    ..Recent studies have suggested that de-acetylation of cyclophilin D (CyPD) by sirtuin 3 (SIRT3) can modulate its binding to the PTP...
  24. 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...
  25. Paillard M, Tubbs E, Thiebaut P, Gomez L, Fauconnier J, Da Silva C, et al. Depressing mitochondria-reticulum interactions protects cardiomyocytes from lethal hypoxia-reoxygenation injury. Circulation. 2013;128:1555-65 pubmed publisher
    ..Accumulation of Ca(2+) into the mitochondrial matrix may activate the mitochondrial chaperone cyclophilin D (CypD) and trigger permeability transition pore opening, whose role in ischemia/reperfusion injury is well ..
  26. Nguyen T, Wong R, Menazza S, Sun J, Chen Y, Wang G, et al. Cyclophilin D modulates mitochondrial acetylome. Circ Res. 2013;113:1308-19 pubmed publisher
    Mice lacking cyclophilin D (CypD(-/-)), a mitochondrial chaperone protein, have altered cardiac metabolism...
  27. 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
  28. 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, ..
  29. 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 ..
  30. Mouri A, Noda Y, Shimizu S, Tsujimoto Y, Nabeshima T. The role of cyclophilin D in learning and memory. Hippocampus. 2010;20:293-304 pubmed publisher
    b>Cyclophilin D (Cyp D) is implicated in cell death pathway and blockade of Cyp D could be a potent therapeutic strategy for degenerative disorders such as Alzheimer's disease, ischemia, and multiple sclerosis, but physiological role of ..
  31. Chen Y, Lewis W, Diwan A, Cheng E, Matkovich S, Dorn G. Dual autonomous mitochondrial cell death pathways are activated by Nix/BNip3L and induce cardiomyopathy. Proc Natl Acad Sci U S A. 2010;107:9035-42 pubmed publisher
    ..of mitochondrial inner membrane potential, Deltapsi(m), and were protected from cell death by cyclosporine A or ppif ablation, implicating the mitochondrial permeability transition pore (MPTP)...
  32. McGee A, Baines C. Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J. 2011;433:119-25 pubmed publisher
    ..However, with the exception of CypD (cyclophilin D), the exact molecular composition of the MPT pore remains uncertain...
  33. Lam C, Zhao W, Liu G, Cai W, Gardner G, Adly G, et al. HAX-1 regulates cyclophilin-D levels and mitochondria permeability transition pore in the heart. Proc Natl Acad Sci U S A. 2015;112:E6466-75 pubmed publisher
    ..Taken together, our findings reveal the role of HAX-1 in regulating cyclophilin-D levels via an Hsp90-dependent mechanism, resulting in protection against activation of mPTP and subsequent cell death responses. ..
  34. Ma T, Gong K, Yan Y, Song B, Zhang X, Gong Y. Mitochondrial modulation of store-operated Ca(2+) entry in model cells of Alzheimer's disease. Biochem Biophys Res Commun. 2012;426:196-202 pubmed publisher
    ..Additionally, treatment with cyclosporin A, a potent inhibitor of cyclophilin D, which can block MPT, could significantly restore the attenuated SOCE in N2a APPwt cells...
  35. 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
    ..Synaptic mitochondria had higher levels of cyclophilin D when compared with nonsynaptic mitochondria, whereas levels of the voltage-dependent anion channel and the ..
  36. Luvisetto S, Basso E, Petronilli V, Bernardi P, Forte M. Enhancement of anxiety, facilitation of avoidance behavior, and occurrence of adult-onset obesity in mice lacking mitochondrial cyclophilin D. Neuroscience. 2008;155:585-96 pubmed publisher
    ..report, we have assessed the behavioral responses of mice missing the Ppif gene (CyPD-KO), encoding mitochondrial cyclophilin D (CyPD)...
  37. 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
    ..Mechanistically, loss of cyclophilin D, a regulator of the mitochondrial permeability transition pore that underpins necrosis, blocked Ca2+ influx-..
  38. 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 ..
  39. Mukherjee R, Mareninova O, Odinokova I, Huang W, Murphy J, Chvanov M, et al. Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP. Gut. 2016;65:1333-46 pubmed publisher
    ..This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. ..
  40. Gainutdinov T, Molkentin J, Siemen D, Ziemer M, Debska Vielhaber G, Vielhaber S, et al. Knockout of cyclophilin D in Ppif⁻/⁻ mice increases stability of brain mitochondria against Ca²⁺ stress. Arch Biochem Biophys. 2015;579:40-6 pubmed publisher
    The mitochondrial peptidyl prolyl isomerase cyclophilin D (CypD) activates permeability transition (PT)...
  41. Daussin F, Godin R, Ascah A, Deschênes S, Burelle Y. Cyclophilin-D is dispensable for atrophy and mitochondrial apoptotic signalling in denervated muscle. J Physiol. 2011;589:855-61 pubmed publisher
    In the present study, we specifically determined whether the regulatory protein cyclophilin-D (CypD), and by extension opening of the permeability transition pore (PTP), is involved in the activation of mitochondria-derived apoptotic ..
  42. Bai F, Fink B, Yu L, Sivitz W. Voltage-Dependent Regulation of Complex II Energized Mitochondrial Oxygen Flux. PLoS ONE. 2016;11:e0154982 pubmed publisher
    ..In summary, we report a previously unrecognized pattern for complex II energized O2 flux. Moreover, our findings suggest that the ADP recycling approach might be more widely adapted for mitochondrial studies. ..
  43. Guo L, Du H, Yan S, Wu X, McKhann G, Chen J, et al. Cyclophilin D deficiency rescues axonal mitochondrial transport in Alzheimer's neurons. PLoS ONE. 2013;8:e54914 pubmed publisher
    ..Here, we report an unexplored role of cyclophilin D (CypD)-dependent mitochondrial permeability transition pore (mPTP) in A?-impaired axonal mitochondrial ..
  44. Laker R, Taddeo E, Akhtar Y, Zhang M, Hoehn K, Yan Z. The Mitochondrial Permeability Transition Pore Regulator Cyclophilin D Exhibits Tissue-Specific Control of Metabolic Homeostasis. PLoS ONE. 2016;11:e0167910 pubmed publisher
    ..b>Cyclophilin D (CypD) is a critical regulator that directly binds to mPTP constituents to facilitate the pore opening...
  45. Kubota M, Kasahara T, Nakamura T, Ishiwata M, Miyauchi T, Kato T. Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial DNA defects. J Neurosci. 2006;26:12314-24 pubmed
    ..mechanism of the altered Ca2+ uptake, we performed DNA microarray analysis and found that the expression of cyclophilin D (CyP-D), a component of the permeability transition pore, was downregulated in the brains of mutPOLG Tg mice...
  46. Parone P, Da Cruz S, Han J, McAlonis Downes M, Vetto A, Lee S, et al. Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis. J Neurosci. 2013;33:4657-71 pubmed publisher
    ..of mitochondrial Ca(2+)-buffering capacity to disease mechanism(s) by eliminating ubiquitous expression of cyclophilin D, a critical regulator of Ca(2+)-mediated opening of the mitochondrial permeability transition pore that ..
  47. Taddeo E, Laker R, Breen D, Akhtar Y, Kenwood B, Liao J, et al. Opening of the mitochondrial permeability transition pore links mitochondrial dysfunction to insulin resistance in skeletal muscle. Mol Metab. 2014;3:124-34 pubmed publisher
    ..a link between mitochondrial dysfunction and insulin resistance by inhibiting the mPTP gatekeeper protein cyclophilin D (CypD) in vivo and in vitro...
  48. Yasuda O, Fukuo K, Sun X, Nishitani M, Yotsui T, Higuchi M, et al. Apop-1, a novel protein inducing cyclophilin D-dependent but Bax/Bak-related channel-independent apoptosis. J Biol Chem. 2006;281:23899-907 pubmed
    ..In contrast, cyclophilin D (CypD), an important component of permeability transition pore-dependent protein release, remains largely ..
  49. Alavian K, Beutner G, Lazrove E, Sacchetti S, Park H, Licznerski P, et al. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc Natl Acad Sci U S A. 2014;111:10580-5 pubmed publisher
    ..Prolonged high matrix Ca(2+) enlarges the c-subunit ring and unhooks it from cyclophilin D/cyclosporine A binding sites in the ATP synthase F1, providing a mechanism for mPTP opening...
  50. Fonai F, Priber J, Jakus P, Kalman N, Antus C, Pollak E, et al. Lack of cyclophilin D protects against the development of acute lung injury in endotoxemia. Biochim Biophys Acta. 2015;1852:2563-73 pubmed publisher
    ..Oxidative stress induces cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT), leading to organ failure in sepsis...
  51. Li B, Chauvin C, De Paulis D, De Oliveira F, Gharib A, Vial G, et al. Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D. Biochim Biophys Acta. 2012;1817:1628-34 pubmed publisher
    ..inhibition than cyclosporin A in tissues that express low levels of the cyclosporin A mitochondrial target, cyclophilin D; and, conversely, that tissues in which rotenone does not affect the PTP are characterized by high levels of ..
  52. Song M, Mihara K, Chen Y, Scorrano L, Dorn G. Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic culling in mouse hearts and cultured fibroblasts. Cell Metab. 2015;21:273-85 pubmed publisher
    ..Drp1, MPTP, and cardiomyocyte mitophagy are functionally integrated. Mitochondrial fission and fusion have opposing roles during in vivo cardiac mitochondrial quality control. ..
  53. Mantel C, O Leary H, Chitteti B, Huang X, Cooper S, Hangoc G, et al. Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock. Cell. 2015;161:1553-65 pubmed publisher
    ..We linked ROS production and induction of the mitochondrial permeability transition pore (MPTP) via cyclophilin D and p53 as mechanisms of EPHOSS...
  54. Osmundsen H, Landin M, From S, Kolltveit K, Risnes S. Changes in gene-expression during development of the murine molar tooth germ. Arch Oral Biol. 2007;52:803-13 pubmed
    ..Such data is therefore useful in directing attention towards genes, or cellular activities, which likely are worthy of further studies as regards their involvement in odontogenesis...
  55. 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
    ..In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered...
  56. Rieusset J, Fauconnier J, Paillard M, Belaidi E, Tubbs E, Chauvin M, et al. Disruption of calcium transfer from ER to mitochondria links alterations of mitochondria-associated ER membrane integrity to hepatic insulin resistance. Diabetologia. 2016;59:614-23 pubmed publisher
    ..We recently identified cyclophilin D (CYPD) as a new partner of this complex and demonstrated a new role for MAMs in the control of insulin's ..
  57. Devalaraja Narashimha K, Diener A, Padanilam B. Cyclophilin D gene ablation protects mice from ischemic renal injury. Am J Physiol Renal Physiol. 2009;297:F749-59 pubmed publisher
    ..b>Cyclophilin D (CypD) is an essential component of MPTP, and recent findings implicate its role in necrotic, but not ..
  58. Allam R, Lawlor K, Yu E, Mildenhall A, Moujalled D, Lewis R, et al. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep. 2014;15:982-90 pubmed publisher
    ..mitochondrial apoptosis BAK and BAX, nor removal of the mitochondrial permeability transition pore component cyclophilin D, nor loss of the mitophagy regulator Parkin, nor deficiency in MAVS affects NLRP3 inflammasome function...
  59. Liu F, Gamez G, Myers D, Clemmons W, Lam W, Jobe S. Mitochondrially mediated integrin ?IIb?3 protein inactivation limits thrombus growth. J Biol Chem. 2013;288:30672-81 pubmed publisher
    ..formation, which is essential for the formation of procoagulant platelets, is impaired in the absence of cyclophilin D (CypD)...
  60. Teixeira G, Abrial M, Portier K, Chiari P, Couture Lepetit E, Tourneur Y, et al. Synergistic protective effect of cyclosporin A and rotenone against hypoxia-reoxygenation in cardiomyocytes. J Mol Cell Cardiol. 2013;56:55-62 pubmed publisher
    ..The matrix protein cyclophilin-D (CypD) is the best-known regulator of mPTP opening...
  61. 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. ..
  62. Hafner A, Dai J, Gomes A, Xiao C, Palmeira C, Rosenzweig A, et al. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY). 2010;2:914-23 pubmed
    ..Here we report that the NAD+-dependent deacetylase SIRT3 deacetylates the regulatory component of the mPTP, cyclophilin D (CypD) on lysine 166, adjacent to the binding site of cyclosporine A, a CypD inhibitor...
  63. Klawitter J, Seres T, Pennington A, Beatty J, Klawitter J, Christians U. Ablation of Cyclophilin D Results in an Activation of FAK, Akt, and ERK Pathways in the Mouse Heart. J Cell Biochem. 2017;118:2933-2940 pubmed publisher
    b>Cyclophilin D (CypD) is a mitochondrial chaperone that regulates the mitochondrial permeability transition pore...
  64. Zhang Z, Wang Y, Yan S, Du F, Yan S. NR2B-dependent cyclophilin D translocation suppresses the recovery of synaptic transmission after oxygen-glucose deprivation. Biochim Biophys Acta. 2015;1852:2225-2234 pubmed publisher
    N-methyl d-aspartate receptor (NMDA) subunit 2B (NR2B)-containing NMDA receptors and mitochondrial protein cyclophilin D (CypD) are well characterized in mediating neuronal death after ischemia, respectively...
  65. Linkermann A, Bräsen J, Darding M, Jin M, Sanz A, Heller J, et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2013;110:12024-9 pubmed publisher
    ..kinase (RIPK)1-mediated necroptosis, but it is currently unclear whether there is one common pathway in which CypD and RIPK1 act in or whether separate RN pathways exist...
  66. Thomas R, Roberts D, Kubli D, Lee Y, Quinsay M, Owens J, et al. Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure. Genes Dev. 2013;27:1365-77 pubmed publisher
    ..Double-knockout mice lacking MCL-1 and cyclophilin D, an essential regulator of the mPTP, exhibited delayed progression to heart failure and extended survival...
  67. Du H, Guo L, Wu X, Sosunov A, McKhann G, Chen J, et al. Cyclophilin D deficiency rescues A?-impaired PKA/CREB signaling and alleviates synaptic degeneration. Biochim Biophys Acta. 2014;1842:2517-27 pubmed publisher
    ..b>Cyclophilin D (CypD), an integral part of mitochondrial permeability transition pore (mPTP), is involved in amyloid beta (A?)..
  68. Vereczki V, Mansour J, Pour Ghaz I, Bodnar I, Pintér O, Zelena D, et al. Cyclophilin D regulates lifespan and protein expression of aging markers in the brain of mice. Mitochondrion. 2017;34:115-126 pubmed publisher
    b>Cyclophilin D (cypD) modulates the properties of the permeability transition pore, a phenomenon implicated in the manifestation of many diseases including aging...
  69. 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 ..
  70. Kang B, Plescia J, Dohi T, Rosa J, Doxsey S, Altieri D. Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network. Cell. 2007;131:257-70 pubmed
    ..These chaperones interact with Cyclophilin D, an immunophilin that induces mitochondrial cell death, and antagonize its function via protein folding/..