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The Mitochondrial Permeability Transition Pore

  • Claudia Morganti
  • Massimo Bonora
  • Luigi Sbano
  • Giampaolo Morciano
  • Giorgio Aquila
  • Gianluca Campo
  • Mariusz R. Wieckowski
  • Carlotta Giorgi
  • Paolo PintonEmail author
Chapter

Abstract

The mitochondrial permeability transition (MPT) consists of an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes, resulting in the osmotic breakout of the organelle. MPT drives cell death and provides an etiological contribution to several human disorders characterized by the acute loss of post-mitotic cells. These conditions include ischemia/reperfusion injury, cancer and neurodegenerative disorders. However, precise knowledge of the structure and regulators of the supramolecular entity that induces MPT, the so-called permeability transition pore complex (PTPC), is lacking and this constitutes a substantial obstacle in the development of MPT-targeting agents with clinical applications. Here we report the current evidences about molecular structure and regulatory components of PTPC. In particular we pay attention on new two proteins which recently were added to the list of PTPC components: the mitochondrial F1FO ATP synthase, particularly and the SPG7 paraplegin matrix AAA peptidase subunit. At least a detailed overview of MPT contribution to pathological condition is provided, focusing on the idea that to develop therapeutic drugs, it will be fundamental to understand the molecular composition of the PTPC.

Keywords

Mitochondrial permeability transition Permeability transition pore complex F1FO ATP synthase Mitochondrial disorders 

Notes

Acknowledgements

P.P. is grateful to Camilla degli Scrovegni for continuous support. P.P. is supported by the Italian Ministry of Education, University and Research (COFIN no. 20129JLHSY_002, FIRB no. RBAP11FXBC_002, and Futuro in Ricerca no. RBFR10EGVP_001), the Italian Cystic Fibrosis Research Foundation (19/2014) and Telethon (GGP15219/B). P.P. and C.G. are supported by local funds from the University of Ferrara and the Italian Association for Cancer Research (IG-18624 and MFAG-13521). M.R.W. is supported by the National Science Center, Poland (grant 2014/15/B/NZ1/00490).

References

  1. Akhabue E, Thiboutot J, Cheng JW, Vittorio TJ, Christodoulidis G, Grady KM, Lerakis S, Kosmas CE (2014) New and emerging risk factors for coronary heart disease. Am J Med Sci 347:151–158PubMedCrossRefGoogle Scholar
  2. Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M, Porter GA Jr, Jonas EA (2014) 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 111:10580–10585PubMedPubMedCentralCrossRefGoogle Scholar
  3. Alcala S, Klee M, Fernandez J, Fleischer A, Pimentel-Muinos FX (2008) A high-throughput screening for mammalian cell death effectors identifies the mitochondrial phosphate carrier as a regulator of cytochrome c release. Oncogene 27:44–54PubMedCrossRefGoogle Scholar
  4. Andreadou I, Iliodromitis EK, Rassaf T, Schulz R, Papapetropoulos A, Ferdinandy P (2015) The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. Br J Pharmacol 172:1587–1606PubMedCrossRefGoogle Scholar
  5. Araszkiewicz A, Grygier M, Lesiak M, Grajek S (2013) The impact of ischemia-reperfusion injury on the effectiveness of primary angioplasty in ST-segment elevation myocardial infarction. Postepy Kardiol Interwencyjnej 9:275–281PubMedPubMedCentralGoogle Scholar
  6. Arbel N, Ben-Hail D, Shoshan-Barmatz V (2012) Mediation of the antiapoptotic activity of Bcl-xL protein upon interaction with VDAC1 protein. J Biol Chem 287:23152–23161PubMedPubMedCentralCrossRefGoogle Scholar
  7. Avkiran M, Marber MS (2002) Na(+)/H(+) exchange inhibitors for cardioprotective therapy: progress, problems and prospects. J Am Coll Cardiol 39:747–753PubMedCrossRefGoogle Scholar
  8. Azoulay-Zohar H, Israelson A, Abu-Hamad S, Shoshan-Barmatz V (2004) In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death. Biochem J 377:347–355PubMedPubMedCentralCrossRefGoogle Scholar
  9. Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (2003) Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92:873–880PubMedPubMedCentralCrossRefGoogle Scholar
  10. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658–662PubMedCrossRefGoogle Scholar
  11. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007) Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9(5):550PubMedPubMedCentralCrossRefGoogle Scholar
  12. Beal MF (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci 23:298–304PubMedCrossRefGoogle Scholar
  13. Beck SJ, Guo L, Phensy A, Tian J, Wang L, Tandon N, Gauba E, Lu L, Pascual JM, Kroener S, Du H (2016) Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer’s disease. Nat Commun 7:11483PubMedPubMedCentralCrossRefGoogle Scholar
  14. Beinlich A, Strohmeier R, Kaufmann M, Kuhl H (2000) Relation of cell proliferation to expression of peripheral benzodiazepine receptors in human breast cancer cell lines. Biochem Pharmacol 60:397–402PubMedCrossRefGoogle Scholar
  15. Bernardi R, Pandolfi PP (2014) A dialog on the first 20 years of PML research and the next 20 ahead. Front Oncol 4:23PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bernardi P, Rasola A, Forte M, Lippe G (2015) The mitochondrial permeability transition pore: channel formation by F-ATP synthase, integration in signal transduction, and role in pathophysiology. Physiol Rev 95:1111–1155PubMedPubMedCentralCrossRefGoogle Scholar
  17. Beutner G, Ruck A, Riede B, Welte W, Brdiczka D (1996) Complexes between kinases, mitochondrial porin and adenylate translocator in rat brain resemble the permeability transition pore. FEBS Lett 396:189–195PubMedCrossRefGoogle Scholar
  18. Beutner G, Ruck A, Riede B, Brdiczka D (1998) Complexes between porin, hexokinase, mitochondrial creatine kinase and adenylate translocator display properties of the permeability transition pore. Implication for regulation of permeability transition by the kinases. Biochim Biophys Acta 1368:7–18PubMedCrossRefGoogle Scholar
  19. Biaglow JE, Miller RA (2005) The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther 4:6–13PubMedCrossRefGoogle Scholar
  20. Bochaton T, Crola-Da-Silva C, Pillot B, Villedieu C, Ferreras L, Alam MR, Thibault H, Strina M, Gharib A, Ovize M, Baetz D (2015) Inhibition of myocardial reperfusion injury by ischemic postconditioning requires sirtuin 3-mediated deacetylation of cyclophilin D. J Mol Cell Cardiol 84:61–69PubMedCrossRefGoogle Scholar
  21. Boland ML, Chourasia AH, Macleod KF (2013) Mitochondrial dysfunction in cancer. Front Oncol 3:292PubMedPubMedCentralCrossRefGoogle Scholar
  22. Bononi A, Bonora M, Marchi S, Missiroli S, Poletti F, Giorgi C, Pandolfi PP, Pinton P (2013) Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner. Cell Death Differ 20:1631–1643PubMedPubMedCentralCrossRefGoogle Scholar
  23. Bonora M, Bononi A, De Marchi E, Giorgi C, Lebiedzinska M, Marchi S, Patergnani S, Rimessi A, Suski JM, Wojtala A, Wieckowski MR, Kroemer G, Galluzzi L, Pinton P (2013) Role of the c subunit of the FO ATP synthase in mitochondrial permeability transition. Cell Cycle 12:674–683PubMedPubMedCentralCrossRefGoogle Scholar
  24. Bonora M, Wieckowski MR, Chinopoulos C, Kepp O, Kroemer G, Galluzzi L, Pinton P (2015) Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition. Oncogene 34:1475–1486PubMedCrossRefGoogle Scholar
  25. Bonora M, Morganti C, Morciano G, Giorgi C, Wieckowski MR, Pinton P (2016) Comprehensive analysis of mitochondrial permeability transition pore activity in living cells using fluorescence-imaging-based techniques. Nat Protoc 11:1067–1080PubMedCrossRefGoogle Scholar
  26. Bonora M, Morganti C, Morciano G, Pedriali G, Lebiedzinska-Arciszewska M, Aquila G, Giorgi C, Rizzo P, Campo G, Ferrari R, Kroemer G, Wieckowski MR, Galluzzi L, Pinton P (2017) Mitochondrial permeability transition involves dissociation of F1Fo ATP synthase dimers and C-ring conformation. EMBO Rep 18(7):1077–1089PubMedCrossRefGoogle Scholar
  27. Brenner C, Grimm S (2006) The permeability transition pore complex in cancer cell death. Oncogene 25:4744–4756PubMedCrossRefGoogle Scholar
  28. Brenner C, Cadiou H, Vieira HL, Zamzami N, Marzo I, Xie Z, Leber B, Andrews D, Duclohier H, Reed JC, Kroemer G (2000) Bcl-2 and Bax regulate the channel activity of the mitochondrial adenine nucleotide translocator. Oncogene 19:329–336PubMedCrossRefGoogle Scholar
  29. Brundin P, Li JY, Holton JL, Lindvall O, Revesz T (2008) Research in motion: the enigma of Parkinson’s disease pathology spread. Nat Rev Neurosci 9:741–745PubMedCrossRefGoogle Scholar
  30. Campanella M, Szabadkai G, Rizzuto R (2008) Modulation of intracellular Ca2+ signalling in HeLa cells by the apoptotic cell death enhancer PK11195. Biochem Pharmacol 76:1628–1636PubMedPubMedCentralCrossRefGoogle Scholar
  31. Chelli B, Falleni A, Salvetti F, Gremigni V, Lucacchini A, Martini C (2001) Peripheral-type benzodiazepine receptor ligands: mitochondrial permeability transition induction in rat cardiac tissue. Biochem Pharmacol 61:695–705PubMedCrossRefGoogle Scholar
  32. Chiara F, Gambalunga A, Sciacovelli M, Nicolli A, Ronconi L, Fregona D, Bernardi P, Rasola A, Trevisan A (2012) Chemotherapeutic induction of mitochondrial oxidative stress activates GSK-3alpha/beta and Bax, leading to permeability transition pore opening and tumor cell death. Cell Death Dis 3:e444PubMedPubMedCentralCrossRefGoogle Scholar
  33. Chiari P, Angoulvant D, Mewton N, Desebbe O, Obadia JF, Robin J, Farhat F, Jegaden O, Bastien O, Lehot JJ, Ovize M (2014) Cyclosporine protects the heart during aortic valve surgery. Anesthesiology 121:232–238PubMedCrossRefGoogle Scholar
  34. Choo YS, Johnson GV, Macdonald M, Detloff PJ, Lesort M (2004) Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet 13:1407–1420PubMedCrossRefGoogle Scholar
  35. Crofts AR, Chappell JB (1965) Calcium ion accumulation and volume changes of isolated liver mitochondria. reversal of calcium ion-induced swelling. Biochem J 95:387–392PubMedPubMedCentralCrossRefGoogle Scholar
  36. Crompton M, Costi A (1990) A heart mitochondrial Ca2(+)-dependent pore of possible relevance to re-perfusion-induced injury. Evidence that ADP facilitates pore interconversion between the closed and open states. Biochem J 266:33–39PubMedPubMedCentralCrossRefGoogle Scholar
  37. Crompton M, Virji S, Ward JM (1998) Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur J Biochem 258:729–735PubMedCrossRefGoogle Scholar
  38. De Marchi U, Basso E, Szabo I, Zoratti M (2006) Electrophysiological characterization of the Cyclophilin D-deleted mitochondrial permeability transition pore. Mol Membr Biol 23:521–530PubMedCrossRefGoogle Scholar
  39. Decaudin D, Castedo M, Nemati F, Beurdeley-Thomas A, De Pinieux G, Caron A, Pouillart P, Wijdenes J, Rouillard D, Kroemer G, Poupon MF (2002) Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo. Cancer Res 62:1388–1393PubMedGoogle Scholar
  40. Demuro A, Parker I, Stutzmann GE (2010) Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 285:12463–12468PubMedPubMedCentralCrossRefGoogle Scholar
  41. Dolder M, Walzel B, Speer O, Schlattner U, Wallimann T (2003) Inhibition of the mitochondrial permeability transition by creatine kinase substrates. Requirement for microcompartmentation. J Biol Chem 278:17760–17766PubMedCrossRefGoogle Scholar
  42. Du H, Guo L, Fang F, Chen D, Sosunov AA, Mckhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD (2008) Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med 14:1097–1105PubMedPubMedCentralCrossRefGoogle Scholar
  43. Duchen MR, Leyssens A, Crompton M (1998) Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single rat cardiomyocytes. J Cell Biol 142:975–988PubMedPubMedCentralCrossRefGoogle Scholar
  44. Dvorakova K, Payne CM, Tome ME, Briehl MM, Vasquez MA, Waltmire CN, Coon A, Dorr RT (2002) Molecular and cellular characterization of imexon-resistant Rpmi8226/I myeloma cells. Mol Cancer Ther 1:185–195PubMedGoogle Scholar
  45. Eguchi Y, Shimizu S, Tsujimoto Y (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 57:1835–1840PubMedGoogle Scholar
  46. Elkamhawy A, Lee J, Park BG, Park I, Pae AN, Roh EJ (2014) Novel quinazoline-urea analogues as modulators for Abeta-induced mitochondrial dysfunction: design, synthesis, and molecular docking study. Eur J Med Chem 84:466–475PubMedCrossRefGoogle Scholar
  47. Elustondo PA, Nichols M, Negoda A, Thirumaran A, Zakharian E, Robertson GS, Pavlov EV (2016) Mitochondrial permeability transition pore induction is linked to formation of the complex of ATPase C-subunit, polyhydroxybutyrate and inorganic polyphosphate. Cell Death Dis 2:16070CrossRefGoogle Scholar
  48. Faure Vigny H, Heddi A, Giraud S, Chautard D, Stepien G (1996) Expression of oxidative phosphorylation genes in renal tumors and tumoral cell lines. Mol Carcinog 16:165–172PubMedCrossRefGoogle Scholar
  49. Forte M, Gold BG, Marracci G, Chaudhary P, Basso E, Johnsen D, Yu X, Fowlkes J, Rahder M, Stem K, Bernardi P, Bourdette D (2007) Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc Natl Acad Sci U S A 104:7558–7563PubMedPubMedCentralCrossRefGoogle Scholar
  50. Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M, Eckle T (2012) Myocardial ischemia reperfusion injury: from basic science to clinical bedside. Semin Cardiothorac Vasc Anesth 16:123–132PubMedPubMedCentralCrossRefGoogle Scholar
  51. Fresno Vara JA, Casado E, De Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M (2004) PI3K/AKT signalling pathway and cancer. Cancer Treat Rev 30:193–204PubMedCrossRefGoogle Scholar
  52. Fulda S, Galluzzi L, Kroemer G (2010) Targeting mitochondria for cancer therapy. Nat Rev Drug Discov 9:447–464PubMedCrossRefGoogle Scholar
  53. Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M, Baehrecke EH, Bazan NG, Bertrand MJ, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Campanella M, Candi E, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, Di Daniele N, Dixit VM, Dynlacht BD, El-Deiry WS, Fimia GM, Flavell RA, Fulda S, Garrido C, Gougeon ML, Green DR, Gronemeyer H, Hajnoczky G, Hardwick JM, Hengartner MO, Ichijo H, Joseph B, Jost PJ, Kaufmann T, Kepp O, Klionsky DJ, Knight RA, Kumar S, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, Lopez-Otin C, Lugli E, Madeo F, Malorni W, Marine JC, Martin SJ, Martinou JC, Medema JP, Meier P, Melino S, Mizushima N, Moll U, Munoz-Pinedo C, Nunez G, Oberst A, Panaretakis T, Penninger JM, Peter ME, Piacentini M, Pinton P, Prehn JH, Puthalakath H, Rabinovich GA, Ravichandran KS, Rizzuto R, Rodrigues CM, Rubinsztein DC, Rudel T, Shi Y, Simon HU, Stockwell BR, Szabadkai G, Tait SW, Tang HL, Tavernarakis N, Tsujimoto Y, Vanden Berghe T, Vandenabeele P, Villunger A, Wagner EF et al (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 22:58–73PubMedCrossRefGoogle Scholar
  54. Garcia JJ, Morales-Rios E, Cortes-Hernandez P, Rodriguez-Zavala JS (2006) The inhibitor protein (IF1) promotes dimerization of the mitochondrial F1F0-ATP synthase. Biochemistry 45:12695–12703PubMedCrossRefGoogle Scholar
  55. Gautier CA, Giaime E, Caballero E, Nunez L, Song Z, Chan D, Villalobos C, Shen J (2012) Regulation of mitochondrial permeability transition pore by PINK1. Mol Neurodegener 7:22PubMedCrossRefGoogle Scholar
  56. Gerle C (2016) On the structural possibility of pore-forming mitochondrial FoF1 ATP synthase. Biochim Biophys Acta 1857:1191–1196PubMedCrossRefGoogle Scholar
  57. Giorgi C, Ito K, Lin HK, Santangelo C, Wieckowski MR, Lebiedzinska M, Bononi A, Bonora M, Duszynski J, Bernardi R, Rizzuto R, Tacchetti C, Pinton P, Pandolfi PP (2010) PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330:1247–1251PubMedPubMedCentralCrossRefGoogle Scholar
  58. Giorgi C, Baldassari F, Bononi A, Bonora M, De Marchi E, Marchi S, Missiroli S, Patergnani S, Rimessi A, Suski JM, Wieckowski MR, Pinton P (2012) Mitochondrial Ca(2+) and apoptosis. Cell Calcium 52:36–43PubMedPubMedCentralCrossRefGoogle Scholar
  59. Giorgi C, Bonora M, Missiroli S, Poletti F, Ramirez FG, Morciano G, Morganti C, Pandolfi PP, Mammano F, Pinton P (2015a) Intravital imaging reveals p53-dependent cancer cell death induced by phototherapy via calcium signaling. Oncotarget 6:1435–1445PubMedGoogle Scholar
  60. Giorgi C, Bonora M, Sorrentino G, Missiroli S, Poletti F, Suski JM, Galindo Ramirez F, Rizzuto R, Di Virgilio F, Zito E, Pandolfi PP, Wieckowski MR, Mammano F, Del Sal G, Pinton P (2015b) p53 at the endoplasmic reticulum regulates apoptosis in a Ca2+-dependent manner. Proc Natl Acad Sci U S A 112:1779–1784PubMedPubMedCentralCrossRefGoogle Scholar
  61. Giorgi C, Missiroli S, Patergnani S, Duszynski J, Wieckowski MR, Pinton P (2015c) Mitochondria-associated membranes: composition, molecular mechanisms, and physiopathological implications. Antioxid Redox Signal 22:995–1019PubMedCrossRefGoogle Scholar
  62. Giorgio V, Bisetto E, Soriano ME, Dabbeni-Sala F, Basso E, Petronilli V, Forte MA, Bernardi P, Lippe G (2009) Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting with the lateral stalk of the complex. J Biol Chem 284:33982–33988PubMedPubMedCentralCrossRefGoogle Scholar
  63. Giorgio V, Von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, Glick GD, Petronilli V, Zoratti M, Szabo I, Lippe G, Bernardi P (2013) Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A 110:5887–5892PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gomez L, Thibault H, Gharib A, Dumont JM, Vuagniaux G, Scalfaro P, Derumeaux G, Ovize M (2007) Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice. Am J Physiol Heart Circ Physiol 293:H1654–H1661PubMedCrossRefGoogle Scholar
  65. Graber HU, Friess H, Zimmermann A, Korc M, Adler G, Schmid R, Buchler MW (1999) Bak expression and cell death occur in peritumorous tissue but not in pancreatic cancer cells. J Gastrointest Surg 3:74–80. discussion 81PubMedCrossRefGoogle Scholar
  66. Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551PubMedPubMedCentralCrossRefGoogle Scholar
  67. Greenamyre JT, Sherer TB, Betarbet R, Panov AV (2001) Complex I and Parkinson’s disease. IUBMB Life 52:135–141PubMedCrossRefGoogle Scholar
  68. Griffiths EJ, Halestrap AP (1995) Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J 307(Pt 1):93–98PubMedPubMedCentralCrossRefGoogle Scholar
  69. Gudnason V, Ingvarsson S, Jonasdottir A, Andresdottir V, Egilsson V (1984) Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue. Int J Cancer 34:63–66PubMedCrossRefGoogle Scholar
  70. Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB (2012) Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid Redox Signal 16:1295–1322PubMedPubMedCentralCrossRefGoogle Scholar
  71. Gutierrez-Aguilar M, Baines CP (2015) Structural mechanisms of cyclophilin D-dependent control of the mitochondrial permeability transition pore. Biochim Biophys Acta 1850:2041–2047PubMedCrossRefGoogle Scholar
  72. Gutierrez-Aguilar M, Douglas DL, Gibson AK, Domeier TL, Molkentin JD, Baines CP (2014) Genetic manipulation of the cardiac mitochondrial phosphate carrier does not affect permeability transition. J Mol Cell Cardiol 72:316–325PubMedPubMedCentralCrossRefGoogle Scholar
  73. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112PubMedCrossRefGoogle Scholar
  74. Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, Sinclair DA (2010) Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY) 2:914–923CrossRefGoogle Scholar
  75. Halestrap AP (2014) The C ring of the F1Fo ATP synthase forms the mitochondrial permeability transition pore: a critical appraisal. Front Oncol 4:234PubMedPubMedCentralCrossRefGoogle Scholar
  76. Halestrap AP, Richardson AP (2015) The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia/reperfusion injury. J Mol Cell Cardiol 78:129–141PubMedCrossRefGoogle Scholar
  77. Hamilton J, Pellman JJ, Brustovetsky T, Harris RA, Brustovetsky N (2015) Oxidative metabolism in YAC128 mouse model of Huntington’s disease. Hum Mol Genet 24:4862–4878PubMedPubMedCentralCrossRefGoogle Scholar
  78. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMedCrossRefGoogle Scholar
  79. Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E, Ankarcrona M (2008) The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105:13145–13150PubMedPubMedCentralCrossRefGoogle Scholar
  80. Haunstetter A, Izumo S (1998) Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res 82:1111–1129PubMedCrossRefGoogle Scholar
  81. Hausenloy DJ, Yellon DM (2013) Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest 123:92–100PubMedPubMedCentralCrossRefGoogle Scholar
  82. Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM (2002) Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55:534–543PubMedCrossRefGoogle Scholar
  83. Hausenloy DJ, Duchen MR, Yellon DM (2003) Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res 60:617–625PubMedCrossRefGoogle Scholar
  84. He J, Ford HC, Carroll J, Ding S, Fearnley IM, Walker JE (2017) Persistence of the mitochondrial permeability transition in the absence of subunit c of human ATP synthase. Proc Natl Acad Sci U S A 114:3409–3414PubMedPubMedCentralCrossRefGoogle Scholar
  85. Hirsch T, Decaudin D, Susin SA, Marchetti P, Larochette N, Resche-Rigon M, Kroemer G (1998) PK11195, a ligand of the mitochondrial benzodiazepine receptor, facilitates the induction of apoptosis and reverses Bcl-2-mediated cytoprotection. Exp Cell Res 241:426–434PubMedCrossRefGoogle Scholar
  86. Izzo V, Bravo-San Pedro JM, Sica V, Kroemer G, Galluzzi L (2016) Mitochondrial permeability transition: new findings and persisting uncertainties. Trends Cell Biol 26:655–667PubMedCrossRefGoogle Scholar
  87. Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL, Olson EN, Sollott SJ (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535–1549PubMedPubMedCentralCrossRefGoogle Scholar
  88. Jung ME, Wilson AM, Ju X, Wen Y, Metzger DB, Simpkins JW (2009) Ethanol withdrawal provokes opening of the mitochondrial membrane permeability transition pore in an estrogen-preventable manner. J Pharmacol Exp Ther 328:692–698PubMedCrossRefGoogle Scholar
  89. Kang BH, Plescia J, Dohi T, Rosa J, Doxsey SJ, Altieri DC (2007) Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network. Cell 131:257–270PubMedCrossRefGoogle Scholar
  90. Karch J, Kwong JQ, Burr AR, Sargent MA, Elrod JW, Peixoto PM, Martinez-Caballero S, Osinska H, Cheng EH, Robbins J, Kinnally KW, Molkentin JD (2013) Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice. Elife 2:e00772PubMedPubMedCentralCrossRefGoogle Scholar
  91. Kawajiri S, Saiki S, Sato S, Hattori N (2011) Genetic mutations and functions of PINK1. Trends Pharmacol Sci 32:573–580PubMedCrossRefGoogle Scholar
  92. Kawamata H, Manfredi G (2010) Mitochondrial dysfunction and intracellular calcium dysregulation in ALS. Mech Ageing Dev 131:517–526PubMedPubMedCentralCrossRefGoogle Scholar
  93. Kepp O, Galluzzi L, Lipinski M, Yuan J, Kroemer G (2011) Cell death assays for drug discovery. Nat Rev Drug Discov 10:221–237PubMedCrossRefGoogle Scholar
  94. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, Macgregor GR, Wallace DC (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427:461–465PubMedPubMedCentralCrossRefGoogle Scholar
  95. Kroemer G (1997) The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 3:614–620PubMedCrossRefGoogle Scholar
  96. Kugler W, Veenman L, Shandalov Y, Leschiner S, Spanier I, Lakomek M, Gavish M (2008) Ligands of the mitochondrial 18 kDa translocator protein attenuate apoptosis of human glioblastoma cells exposed to erucylphosphohomocholine. Cell Oncol 30:435–450PubMedPubMedCentralGoogle Scholar
  97. Kvietys PR, Granger DN (2012) Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 52:556–592PubMedCrossRefGoogle Scholar
  98. Kwong JQ, Davis J, Baines CP, Sargent MA, Karch J, Wang X, Huang T, Molkentin JD (2014) Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy. Cell Death Differ 21:1209–1217PubMedPubMedCentralCrossRefGoogle Scholar
  99. Lamarche F, Carcenac C, Gonthier B, Cottet-Rousselle C, Chauvin C, Barret L, Leverve X, Savasta M, Fontaine E (2013) Mitochondrial permeability transition pore inhibitors prevent ethanol-induced neuronal death in mice. Chem Res Toxicol 26:78–88PubMedCrossRefGoogle Scholar
  100. Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 5:958–963PubMedPubMedCentralCrossRefGoogle Scholar
  101. Leal SS, Gomes CM (2015) Calcium dysregulation links ALS defective proteins and motor neuron selective vulnerability. Front Cell Neurosci 9:225PubMedPubMedCentralCrossRefGoogle Scholar
  102. Lemasters JJ (1999) The mitochondrial permeability transition and the calcium, oxygen and pH paradoxes: one paradox after another. Cardiovasc Res 44(3):470PubMedCrossRefGoogle Scholar
  103. Lemasters JJ, Bond JM, Chacon E, Harper IS, Kaplan SH, Ohata H, Trollinger DR, Herman B, Cascio WE (1996) The pH paradox in ischemia-reperfusion injury to cardiac myocytes. EXS 76:99–114PubMedGoogle Scholar
  104. Leung AW, Varanyuwatana P, Halestrap AP (2008) The mitochondrial phosphate carrier interacts with cyclophilin D and may play a key role in the permeability transition. J Biol Chem 283:26312–26323PubMedPubMedCentralCrossRefGoogle Scholar
  105. Leung CH, Wang L, Nielsen JM, Tropak MB, Fu YY, Kato H, Callahan J, Redington AN, Caldarone CA (2014) Remote cardioprotection by transfer of coronary effluent from ischemic preconditioned rabbit heart preserves mitochondrial integrity and function via adenosine receptor activation. Cardiovasc Drugs Ther 28:7–17PubMedCrossRefGoogle Scholar
  106. Lezi E, Swerdlow RH (2012) Mitochondria in neurodegeneration. Adv Exp Med Biol 942:269–286PubMedPubMedCentralCrossRefGoogle Scholar
  107. Locasale JW, Cantley LC (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metab 14:443–451PubMedPubMedCentralCrossRefGoogle Scholar
  108. Lu X, Kwong JQ, Molkentin JD, Bers DM (2016) Individual cardiac mitochondria undergo rare transient permeability transition pore openings. Circ Res 118:834–841PubMedCrossRefGoogle Scholar
  109. Luth ES, Stavrovskaya IG, Bartels T, Kristal BS, Selkoe DJ (2014) Soluble, prefibrillar alpha-synuclein oligomers promote complex I-dependent, Ca2+-induced mitochondrial dysfunction. J Biol Chem 289:21490–21507PubMedPubMedCentralCrossRefGoogle Scholar
  110. Maaser K, Hopfner M, Jansen A, Weisinger G, Gavish M, Kozikowski AP, Weizman A, Carayon P, Riecken EO, Zeitz M, Scherubl H (2001) Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells. Br J Cancer 85:1771–1780PubMedPubMedCentralCrossRefGoogle Scholar
  111. Marchetti P, Castedo M, Susin SA, Zamzami N, Hirsch T, Macho A, Haeffner A, Hirsch F, Geuskens M, Kroemer G (1996) Mitochondrial permeability transition is a central coordinating event of apoptosis. J Exp Med 184:1155–1160PubMedCrossRefGoogle Scholar
  112. Marchi S, Patergnani S, Pinton P (2014) The endoplasmic reticulum-mitochondria connection: one touch, multiple functions. Biochim Biophys Acta 1837:461–469PubMedCrossRefGoogle Scholar
  113. Martel C, Huynh le H, Garnier A, Ventura-Clapier R, Brenner C (2012) Inhibition of the mitochondrial permeability transition for cytoprotection: direct versus indirect mechanisms. Biochem Res Int 2012:213403PubMedPubMedCentralCrossRefGoogle Scholar
  114. Martin LJ, Gertz B, Pan Y, Price AC, Molkentin JD, Chang Q (2009) The mitochondrial permeability transition pore in motor neurons: involvement in the pathobiology of ALS mice. Exp Neurol 218:333–346PubMedPubMedCentralCrossRefGoogle Scholar
  115. Martin LJ, Semenkow S, Hanaford A, Wong M (2014) Mitochondrial permeability transition pore regulates Parkinson’s disease development in mutant alpha-synuclein transgenic mice. Neurobiol Aging 35:1132–1152PubMedCrossRefGoogle Scholar
  116. Marzo I, BRENNER C, Zamzami N, Jurgensmeier JM, Susin SA, Vieira HL, Prevost MC, Xie Z, Matsuyama S, Reed JC, Kroemer G (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281:2027–2031PubMedCrossRefGoogle Scholar
  117. Mcenery MW, Snowman AM, Trifiletti RR, Snyder SH (1992) Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. Proc Natl Acad Sci U S A 89:3170–3174PubMedPubMedCentralCrossRefGoogle Scholar
  118. Milakovic T, Quintanilla RA, Johnson GV (2006) Mutant huntingtin expression induces mitochondrial calcium handling defects in clonal striatal cells: functional consequences. J Biol Chem 281:34785–34795PubMedCrossRefGoogle Scholar
  119. Moe GW, Marin-Garcia J (2016) Role of cell death in the progression of heart failure. Heart Fail Rev 21:157–167PubMedCrossRefGoogle Scholar
  120. Morciano G, Giorgi C, Bonora M, Punzetti S, Pavasini R, Wieckowski MR, Campo G, Pinton P (2015) Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury. J Mol Cell Cardiol 78:142–153PubMedCrossRefGoogle Scholar
  121. Morciano G, Bonora M, Giorgi C, Pinton P (2017) Other bricks for the correct construction of the mitochondrial permeability transition pore complex. Cell Death Dis 8:e2698PubMedPubMedCentralCrossRefGoogle Scholar
  122. Mukhin AG, Papadopoulos V, Costa E, Krueger KE (1989) Mitochondrial benzodiazepine receptors regulate steroid biosynthesis. Proc Natl Acad Sci U S A 86:9813–9816PubMedPubMedCentralCrossRefGoogle Scholar
  123. Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A 95:14681–14686PubMedPubMedCentralCrossRefGoogle Scholar
  124. Neuhof C, Neuhof H (2014) Calpain system and its involvement in myocardial ischemia and reperfusion injury. World J Cardiol 6:638–652PubMedPubMedCentralCrossRefGoogle Scholar
  125. Nishihara M, Miura T, Miki T, Tanno M, Yano T, Naitoh K, Ohori K, Hotta H, Terashima Y, Shimamoto K (2007) Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection. J Mol Cell Cardiol 43:564–570PubMedCrossRefGoogle Scholar
  126. Palmieri F (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch 447:689–709PubMedCrossRefGoogle Scholar
  127. Pani G, Colavitti R, Bedogni B, Fusco S, Ferraro D, Borrello S, Galeotti T (2004) Mitochondrial superoxide dismutase: a promising target for new anticancer therapies. Curr Med Chem 11:1299–1308PubMedCrossRefGoogle Scholar
  128. Pastorino JG, Hoek JB (2003) Hexokinase II: the integration of energy metabolism and control of apoptosis. Curr Med Chem 10:1535–1551PubMedCrossRefGoogle Scholar
  129. Pastorino JG, Hoek JB (2008) Regulation of hexokinase binding to VDAC. J Bioenerg Biomembr 40:171–182PubMedPubMedCentralCrossRefGoogle Scholar
  130. Pastorino JG, Simbula G, Gilfor E, Hoek JB, Farber JL (1994) Protoporphyrin IX, an endogenous ligand of the peripheral benzodiazepine receptor, potentiates induction of the mitochondrial permeability transition and the killing of cultured hepatocytes by rotenone. J Biol Chem 269:31041–31046PubMedGoogle Scholar
  131. Pastorino JG, Hoek JB, Shulga N (2005) Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res 65:10545–10554PubMedCrossRefGoogle Scholar
  132. Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Giorgi C, Marchi S, Missiroli S, Poletti F, Rimessi A, Duszynski J, Wieckowski MR, Pinton P (2011) Calcium signaling around Mitochondria Associated Membranes (MAMs). Cell Commun Signal 9:19PubMedPubMedCentralCrossRefGoogle Scholar
  133. Pauleau AL, Galluzzi L, Scholz SR, Larochette N, Kepp O, Kroemer G (2008) Unexpected role of the phosphate carrier in mitochondrial fragmentation. Cell Death Differ 15:616–618PubMedCrossRefGoogle Scholar
  134. Pediaditakis P, Kim JS, He L, Zhang X, Graves LM, Lemasters JJ (2010) Inhibition of the mitochondrial permeability transition by protein kinase A in rat liver mitochondria and hepatocytes. Biochem J 431:411–421PubMedPubMedCentralCrossRefGoogle Scholar
  135. Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di Virgilio F, Pozzan T, Rizzuto R (2000) Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in Bcl-2-overexpressing cells. J Cell Biol 148:857–862PubMedPubMedCentralCrossRefGoogle Scholar
  136. Piper HM, Meuter K, Schafer C (2003) Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg 75:S644–S648PubMedCrossRefGoogle Scholar
  137. Pogoryelov D, Klyszejko AL, Krasnoselska GO, Heller EM, Leone V, Langer JD, Vonck J, Muller DJ, Faraldo-Gomez JD, Meier T (2012) Engineering rotor ring stoichiometries in the ATP synthase. Proc Natl Acad Sci U S A 109:E1599–E1608PubMedPubMedCentralCrossRefGoogle Scholar
  138. Pulido R, Baker SJ, Barata JT, Carracedo A, Cid VJ, Chin-Sang ID, Dave V, Den Hertog J, Devreotes P, Eickholt BJ, Eng C, Furnari FB, Georgescu MM, Gericke A, Hopkins B, Jiang X, Lee SR, Losche M, Malaney P, Matias-Guiu X, Molina M, Pandolfi PP, Parsons R, Pinton P, Rivas C, Rocha RM, Rodriguez MS, Ross AH, Serrano M, Stambolic V, Stiles B, Suzuki A, Tan SS, Tonks NK, Trotman LC, Wolff N, Woscholski R, Wu H, Leslie NR (2014) A unified nomenclature and amino acid numbering for human PTEN. Sci Signal 7:pe15PubMedPubMedCentralCrossRefGoogle Scholar
  139. Quinn BA, Dash R, Azab B, Sarkar S, Das SK, Kumar S, Oyesanya RA, Dasgupta S, Dent P, Grant S, Rahmani M, Curiel DT, Dmitriev I, Hedvat M, Wei J, Wu B, Stebbins JL, Reed JC, Pellecchia M, Sarkar D, Fisher PB (2011) Targeting Mcl-1 for the therapy of cancer. Expert Opin Investig Drugs 20:1397–1411PubMedPubMedCentralCrossRefGoogle Scholar
  140. Quintanilla RA, Tapia C, Perez MJ (2017) Possible role of mitochondrial permeability transition pore in the pathogenesis of Huntington disease. Biochem Biophys Res Commun 483:1078–1083PubMedCrossRefGoogle Scholar
  141. Rao VK, Carlson EA, Yan SS (2014) Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochim Biophys Acta 1842:1267–1272PubMedCrossRefGoogle Scholar
  142. Rasheed MZ, Tabassum H, Parvez S (2017) Mitochondrial permeability transition pore: a promising target for the treatment of Parkinson’s disease. Protoplasma 254:33–42PubMedCrossRefGoogle Scholar
  143. Rasola A, Bernardi P (2011) Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis. Cell Calcium 50:222–233PubMedCrossRefGoogle Scholar
  144. Rasola A, Sciacovelli M, Pantic B, Bernardi P (2010) Signal transduction to the permeability transition pore. FEBS Lett 584:1989–1996PubMedPubMedCentralCrossRefGoogle Scholar
  145. Rempel A, Mathupala SP, Griffin CA, Hawkins AL, Pedersen PL (1996) Glucose catabolism in cancer cells: amplification of the gene encoding type II hexokinase. Cancer Res 56:2468–2471PubMedGoogle Scholar
  146. Rimessi A, Patergnani S, Bonora M, Wieckowski MR, Pinton P (2015) Mitochondrial Ca(2+) remodeling is a prime factor in oncogenic behavior. Front Oncol 5:143PubMedPubMedCentralCrossRefGoogle Scholar
  147. Roy SS, Madesh M, Davies E, Antonsson B, Danial N, Hajnoczky G (2009) Bad targets the permeability transition pore independent of Bax or Bak to switch between Ca2+-dependent cell survival and death. Mol Cell 33:377–388PubMedPubMedCentralCrossRefGoogle Scholar
  148. Savino C, Pelicci P, Giorgio M (2013) The P66Shc/mitochondrial permeability transition pore pathway determines neurodegeneration. Oxid Med Cell Longev 2013:719407PubMedPubMedCentralCrossRefGoogle Scholar
  149. Sayeed I, Parvez S, Winkler-Stuck K, Seitz G, Trieu I, Wallesch CW, Schonfeld P, Siemen D (2006) Patch clamp reveals powerful blockade of the mitochondrial permeability transition pore by the D2-receptor agonist pramipexole. FASEB J 20:556–558PubMedCrossRefGoogle Scholar
  150. Schonfeld P, Siemen D, Kreutzmann P, Franz C, Wojtczak L (2013) Interaction of the antibiotic minocycline with liver mitochondria—role of membrane permeabilization in the impairment of respiration. FEBS J 280:6589–6599PubMedCrossRefGoogle Scholar
  151. Seaton TA, Cooper JM, Schapira AH (1998) Cyclosporin inhibition of apoptosis induced by mitochondrial complex I toxins. Brain Res 809:12–17PubMedCrossRefGoogle Scholar
  152. Shanmughapriya S, Rajan S, Hoffman NE, Higgins AM, Tomar D, Nemani N, Hines KJ, Smith DJ, Eguchi A, Vallem S, Shaikh F, Cheung M, Leonard NJ, Stolakis RS, Wolfers MP, Ibetti J, Chuprun JK, Jog NR, Houser SR, Koch WJ, Elrod JW, Madesh M (2015) SPG7 is an essential and conserved component of the mitochondrial permeability transition pore. Mol Cell 60:47–62PubMedPubMedCentralCrossRefGoogle Scholar
  153. Shargorodsky L, Veenman L, Caballero B, Pe’er Y, Leschiner S, Bode J, Gavish M (2012) The nitric oxide donor sodium nitroprusside requires the 18 kDa Translocator Protein to induce cell death. Apoptosis 17:647–665PubMedCrossRefGoogle Scholar
  154. Sharma R, Randhawa PK, Singh N, Jaggi AS (2015) Bradykinin in ischemic conditioning-induced tissue protection: evidences and possible mechanisms. Eur J Pharmacol 768:58–70PubMedCrossRefGoogle Scholar
  155. Shimizu S, Narita M, Tsujimoto Y (1999) Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 399:483–487PubMedCrossRefGoogle Scholar
  156. Shinohara Y, Shima A, Kamida M, Terada H (1991) Uncoupling protein is expressed in liver mitochondria of cold-exposed and newborn rats. FEBS Lett 293:173–174PubMedCrossRefGoogle Scholar
  157. Shinohara Y, Ishida T, Hino M, Yamazaki N, Baba Y, Terada H (2000) Characterization of porin isoforms expressed in tumor cells. Eur J Biochem 267:6067–6073PubMedCrossRefGoogle Scholar
  158. Shintani-Ishida K, Yoshida K (2015) Mitochondrial m-calpain opens the mitochondrial permeability transition pore in ischemia-reperfusion. Int J Cardiol 197:26–32PubMedCrossRefGoogle Scholar
  159. Singh P, Suman S, Chandna S, Das TK (2009) Possible role of amyloid-beta, adenine nucleotide translocase and cyclophilin-D interaction in mitochondrial dysfunction of Alzheimer’s disease. Bioinformation 3:440–445PubMedPubMedCentralCrossRefGoogle Scholar
  160. Slomovitz BM, Coleman RL (2012) The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res 18:5856–5864PubMedCrossRefGoogle Scholar
  161. Stys PK, Zamponi GW, Van Minnen J, Geurts JJ (2012) Will the real multiple sclerosis please stand up? Nat Rev Neurosci 13:507–514PubMedCrossRefGoogle Scholar
  162. Su KG, Banker G, Bourdette D, Forte M (2009) Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis. Curr Neurol Neurosci Rep 9:411–417PubMedPubMedCentralCrossRefGoogle Scholar
  163. Sun J, Nguyen T, Aponte AM, Menazza S, Kohr MJ, Roth DM, Patel HH, Murphy E, Steenbergen C (2015) Ischaemic preconditioning preferentially increases protein S-nitrosylation in subsarcolemmal mitochondria. Cardiovasc Res 106:227–236PubMedPubMedCentralCrossRefGoogle Scholar
  164. Takuma K, Phuagphong P, Lee E, Mori K, Baba A, Matsuda T (2001) Anti-apoptotic effect of cGMP in cultured astrocytes: inhibition by cGMP-dependent protein kinase of mitochondrial permeable transition pore. J Biol Chem 276:48093–48099PubMedCrossRefGoogle Scholar
  165. Tanveer A, Virji S, Andreeva L, Totty NF, Hsuan JJ, Ward JM, Crompton M (1996) Involvement of cyclophilin D in the activation of a mitochondrial pore by Ca2+ and oxidant stress. Eur J Biochem 238:166–172PubMedCrossRefGoogle Scholar
  166. Tedeschi H, Hegarty HJ, James JM (1965) Osmotic reversal of phosphate-induced mitochondrial swelling. Biochim Biophys Acta 104:612–615PubMedCrossRefGoogle Scholar
  167. Thomas RL, Roberts DJ, Kubli DA, Lee Y, Quinsay MN, Owens JB, Fischer KM, Sussman MA, Miyamoto S, Gustafsson AB (2013) Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure. Genes Dev 27:1365–1377PubMedPubMedCentralCrossRefGoogle Scholar
  168. Traba J, Del Arco A, Duchen MR, Szabadkai G, Satrustegui J (2012) SCaMC-1 promotes cancer cell survival by desensitizing mitochondrial permeability transition via ATP/ADP-mediated matrix Ca(2+) buffering. Cell Death Differ 19:650–660PubMedCrossRefGoogle Scholar
  169. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160PubMedCrossRefGoogle Scholar
  170. Vander Heiden MG, Chandel NS, Schumacker PT, Thompson CB (1999) Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. Mol Cell 3:159–167PubMedCrossRefGoogle Scholar
  171. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM (2012) p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 149:1536–1548PubMedPubMedCentralCrossRefGoogle Scholar
  172. Verma M, Shulga N, Pastorino JG (2013) Sirtuin-4 modulates sensitivity to induction of the mitochondrial permeability transition pore. Biochim Biophys Acta 1827:38–49PubMedCrossRefGoogle Scholar
  173. Verrier F, Deniaud A, Lebras M, Metivier D, Kroemer G, Mignotte B, Jan G, Brenner C (2004) Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis. Oncogene 23:8049–8064PubMedCrossRefGoogle Scholar
  174. Wallimann T, Dolder M, Schlattner U, Eder M, Hornemann T, O’Gorman E, Ruck A, Brdiczka D (1998) Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology. Biofactors 8:229–234PubMedCrossRefGoogle Scholar
  175. Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8:519–530PubMedPubMedCentralCrossRefGoogle Scholar
  176. Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206:2049–2057PubMedCrossRefGoogle Scholar
  177. Winklhofer KF, Haass C (2010) Mitochondrial dysfunction in Parkinson’s disease. Biochim Biophys Acta 1802:29–44PubMedCrossRefGoogle Scholar
  178. Wolin EM (2013) PI3K/Akt/mTOR pathway inhibitors in the therapy of pancreatic neuroendocrine tumors. Cancer Lett 335:1–8PubMedCrossRefGoogle Scholar
  179. Yang Y, Karakhanova S, Werner J, Bazhin AV (2013) Reactive oxygen species in cancer biology and anticancer therapy. Curr Med Chem 20:3677–3692PubMedCrossRefGoogle Scholar
  180. Yoshida M, Muneyuki E, Hisabori T (2001) ATP synthase—a marvellous rotary engine of the cell. Nat Rev Mol Cell Biol 2:669–677PubMedCrossRefGoogle Scholar
  181. Youdim MB, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T (2005) Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res 79:172–179PubMedCrossRefGoogle Scholar
  182. Zamzami N, El Hamel C, Maisse C, Brenner C, Munoz-Pinedo C, Belzacq AS, Costantini P, Vieira H, Loeffler M, Molle G, Kroemer G (2000) Bid acts on the permeability transition pore complex to induce apoptosis. Oncogene 19:6342–6350PubMedCrossRefGoogle Scholar
  183. Zheng Y, Shi Y, Tian C, Jiang C, Jin H, Chen J, Almasan A, Tang H, Chen Q (2004) Essential role of the voltage-dependent anion channel (VDAC) in mitochondrial permeability transition pore opening and cytochrome c release induced by arsenic trioxide. Oncogene 23:1239–1247PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Claudia Morganti
    • 1
    • 2
  • Massimo Bonora
    • 1
    • 2
  • Luigi Sbano
    • 1
    • 2
  • Giampaolo Morciano
    • 1
    • 2
  • Giorgio Aquila
    • 3
  • Gianluca Campo
    • 4
  • Mariusz R. Wieckowski
    • 5
  • Carlotta Giorgi
    • 1
    • 2
  • Paolo Pinton
    • 1
    • 2
    Email author
  1. 1.Section of General Pathology, Department of Morphology, Surgery and Experimental MedicineUniversity of FerraraFerraraItaly
  2. 2.Laboratory for Technologies of Advanced Therapies (LTTA)University of FerraraFerraraItaly
  3. 3.Department of Morphology, Surgery and Experimental MedicineUniversity of FerraraFerraraItaly
  4. 4.Cardiovascular InstituteUniversity of FerraraFerraraItaly
  5. 5.Department of BiochemistryNencki Institute of Experimental BiologyWarsawPoland

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