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Gambalunga, Alberto (2008) Identificazione e caratterizzazione di nuovi inibitori del poro della transizione della permeabilità  mitocondriale. [Ph.D. thesis]

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Abstract (english)

We have characterized the mitochondrial and cellular effects of two molecules identified by Genextra's S.p.A from a chemical library by high throughput screening (HTS) designed to identify novel inhibitors of the mitochondrial permeability transition pore (PTP). The screening, based on in vitro calcium-induced mitochondrial swelling, yielded several PTP inhibitory compounds and two of them, CngPtP003 and CngPtP006, have been selected for the present study. We studied the inhibitory properties of CngPtP003 and CngPtP006 on PTP in isolated mouse liver mitochondria with the Calcium Retention Capacity (CRC) assay, and the inhibitory profiles compared with those displayed by the well known PTP inhibitor cyclosporin A (CsA). From this first set of experiments we confirmed that both compounds are PTP inhibitors with different biological potency and efficacy, and that their molecular targets are not the same as that of CsA, with which both compounds displayed additive effects. In a second set of experiments we studied the mitochondrial effects of CngPtP003 and CngPtP006 in intact HeLa cells with the tetramethylrhodamine methyl ester (TMRM) assay, which measures the mitochondrial membrane potential. We found that only CngPtP003 is able to protect the cells from the depolarization and from cell death caused by the PTP inducer arachidonic acid. Lack of inhibition by CngPtP006 data has been confirmed both in HeLa isolated mitochondria and in several human permeabilized cell lines, indicating that the inhibitory properties of CngPtP006 are limited to mouse mitochondria, which were used in the primary screening. These results validate the HTS approach for the identification of novel PTP inhibitors, whose suitability for drug development is currently under investigation.

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EPrint type:Ph.D. thesis
Tutor:Bernardi, Paolo
Ph.D. course:Ciclo 20 > Scuole per il 20simo ciclo > BIOSCIENZE > BIOLOGIA CELLULARE
Data di deposito della tesi:31 January 2008
Anno di Pubblicazione:31 January 2008
Key Words:PTP, mitocondri, inibitori
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/09 Fisiologia
Struttura di riferimento:Centri > Centro Interdipartimentale di servizi A. Vallisneri
Dipartimenti > pre 2012 - Dipartimento di Scienze Biomediche Sperimentali
Codice ID:284
Depositato il:02 Oct 2008
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1. Alnemri,E.S., Livingston, D.J., Nicholson, D.W., Salvesen, G., Thornberry, N.A., Wong, W.W., and Yuan, J. (1996). Human ICE/CED-3 protease nomenclature. Cell 87:171.+ Cerca con Google

2. Andrabi S.A., Sayeed I., Siemen D., Wolf G. and Horn T.F. (2004) Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J 18, 869–871. Cerca con Google

3. Anflous K., Armstrong D.D., Craigen W.J. (2001) Altered mitochondrial sensitivity for ADP and maintenance of creatine-stimulated respiration in oxidative striated muscles from VDAC1-deficient mice. J Biol Chem. Jan 19;276(3):1954 60. Cerca con Google

4. Angelin A., Tiepolo T., Sabatelli P., Grumati P., Bergamin N., Golfieri C., Mattioli E., Gualandi F., Ferlini A., Merlini L., Maraldi N.M., Bonaldo P., Bernardi P. (2007) Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins. Proc Natl Acad Sci U S A. Jan 16;104(3):991-6 Cerca con Google

5. Anholt R.R., Pedersen P.L., De Souza E.B. and Snyder S.H. (1986) The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane. J Biol Chem 261, 576–583. Cerca con Google

6. Ankarcrona M., Dypbukt J.M., Bonfoco E., Zhivotovsky B., Orrenius S., Lipton S.A., Nicotera P. (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron. Oct;15(4):961-73. Cerca con Google

7. Argaud L., Gateau-Roesch O., Muntean D., Chalabreysse L., Loufouat J., Robert D. and Ovize M. (2005) Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. J Mol Cell Cardiol 38, 367–374. Cerca con Google

8. Baines C.P., Kaiser R.A., Purcell N.H., Blair N.S., Osinska H., Hambleton M.A., Brunskill E.W., Sayen M.R., Gottlieb R.A., Dorn G.W. et al. (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434, 658–662. Cerca con Google

9. Baines C.P., Kaiser R.A., Sheiko T., Craigen W.J., Molkentin J.D. (2007) Voltage-dependent anion channels are dispensable for mitochondrialdependent cell death. Nat Cell Biol. May;9(5):550-5. Cerca con Google

10. Basso E., Fante L., Fowlkes J., Petronilli V., Forte M.A., Bernardi P. (2005), Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D. J Biol Chem. May 13;280(19):18558-61. Cerca con Google

11. Bernardi,P. (1999). Mitochondrial transport of cations: Channels, exchangers and permeability transition. Physiol. Rev. 79, 1127-1155. Cerca con Google

12. Bernardi,P., Vassanelli,S., Veronese,P., Colonna,R., Szabo,I., and Zoratti,M. (1992). Modulation of the mitochondrial permeability transition pore. Effect of protons and divalent cations. J. Biol. Chem. 267, 2934-2939. Cerca con Google

13. Bernardi P. (1992) Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by the proton electrochemical gradient. Evidence that the pore can be opened by membrane depolarization. J Biol Chem 267, 8834–8839. Cerca con Google

14. Bernardi P., Krauskopf A., Basso E., Petronilli V., Blachly-Dyson E., Di Lisa F., Forte M.A. (2006) The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J. May;273(10):2077-99. Cerca con Google

15. Bernardi,P., Broekemeier,K.M., and Pfeiffer,D.R. (1994). Recent progress on regulation of the mitochondrial permeability transition pore; a cyclosporinsensitive pore in the inner mitochondrial membrane. J. Bioenerg. Biomembr. 26, 509-517. Cerca con Google

16. Bernardi P. and Azzone G.F. (1981) Cytochrome c as an electron shuttle between the outer and inner mitochondrial membranes. J Biol Chem 256, 7187–7192. Cerca con Google

17. Bernardi,P., Petronilli,V., Di Lisa F., and Forte,M. (2001). A mitochondrial perspective on cell death. Trends Biochem. Sci. 26, 112-117. Cerca con Google

18. Berson A., Descatoire V., Sutton A., Fau D., Maulny B., Vadrot N., Feldmann G., Berthon B., Tordjmann T. and Pessayre D. (2001) Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not zolpidem, in rat hepatocytes: role of mitochondrial permeability transition and metabolic activation. J Pharmacol Exp Ther 299, 793–800. Cerca con Google

19. Bonaldo P., Braghetta P., Zanetti M., Piccolo S., Volpin D. and Bressan G.M. (1998) Collagen VI deficiency induces early onset myopathy in the mouse: an animal model for Bethlem myopathy. Hum Mol Genet 7, 2135–2140. Cerca con Google

20. Bond J.M., Herman B. and Lemasters J.J. (1991) Protection by acidotic pH against anoxia / reoxygenation injury to rat neonatal cardiac myocytes. Biochem Biophys Res Commun 179, 798–803. Cerca con Google

21. Bond J.M., Chacon E., Herman B. and Lemasters J.J. (1993) Intracellular pH and Ca2+ homeostasis in the pH paradox of reperfusion injury to neonatal rat cardiac myocytes. Am J Physiol 265, C129–C137. Cell Cardiol 38, 367–374. Cerca con Google

22. Bono F., Lamarche I., Prabonnaud V., Le Fur G. & Herbert J.M. (1999) Peripheral benzodiazepine receptor agonists exhibit potent antiapoptotic activities. Biochem Biophys Res Commun 265, 457–461. Cerca con Google

23. Brash,A.R. (2001). Arachidonic acid as a bioactive molecule. J. Clin. Invest 107, 1339-1345. Cerca con Google

24. Broekemeier,K.M., Dempsey,M.E., and Pfeiffer,D.R. (1989). Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J. Biol. Chem. 264, 7826-7830. Cerca con Google

25. Camacho Vanegas O., Bertini E., Zhang R.Z., Petrini S., Minosse C., Sabatelli P., Giusti B., Chu M.L. and Pepe G. (2001) Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI. Proc Natl Acad Sci USA 98, 7516–7521. Cerca con Google

26. Cesura A.M., Pinard E., Schubenel R., Goetschy V., Friedlein A., Langen H., Polcic P., Forte M.A., Bernardi P. and Kemp J.A. (2003) The voltagedependent anion channel is the target for a new class of inhibitors of the mitochondrial permeability transition pore. J Biol Chem 278, 49812–49818. Cerca con Google

27. Chernyak B.V., Bernardi P. (1996) The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur J Biochem. Jun 15;238(3):623 30. Cerca con Google

28. Clarke S.J., McStay G.P. and Halestrap A.P. (2002) Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A. J Biol Chem 277, 34793– 34799. Cerca con Google

29. Connern C.P. and Halestrap A.P. (1992) 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 284, 381–385. Cerca con Google

30. Costantini,P., Chernyak,B.V., Petronilli,V., and Bernardi,P. (1996). Modulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites. J. Biol. Chem. 271, 6746-6751 Cerca con Google

31. Costantini P., Colonna R. and Bernardi P. (1998) Induction of the mitochondrial permeability transition pore by N-ethylmaleimide depends on secondary oxidation of critical thiol groups. Potentiation by copperorthophenanthroline without dimerization of the adenine nucleotide Cerca con Google

32. translocase. Biochim Biophys Acta 1365,385–392. Cerca con Google

33. Crompton M. (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341, 233–249. Cerca con Google

34. Crompton,M., Costi,A., and Hayat,L. (1987). Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria [published erratum appears in Biochem J 1987 Sep 15;246(3):following 806]. . Biochem. J. 245, 915-918. Cerca con Google

35. Crompton M., Virji S. and Ward J.M. (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, 729–735. Cerca con Google

36. Desagher S., Martinou J.C. (2000) Mitochondria as the central control point of apoptosis. Trends Cell Biol. Sep;10(9):369-77. Cerca con Google

37. Di Lisa F., Menabo` R., Canton M. and Petronilli V. (1998) The role of mitochondria in the salvage and the injury of the ischemic myocardium. Biochim Biophys Acta 1366, 69–78. Cerca con Google

38. Di Lisa F. and Bernardi,P. (1998). Mitochondrial function as a determinant of recovery or death in cell response to injury. Mol. Cell Biochem. 184, 379-391. Cerca con Google

39. Du,C., Fang,M., Li,Y., Li,L., and Wang,X. (2000). Smac, a mitochondrial protein that promotes cytochrome c - dependent caspase activation by eliminating IAP inhibition. Cell 102, 33-42. Cerca con Google

40. Ekert,P.G., Silke,J., Connolly,L.M., Reid,G.E., Moritz,R.L., and Vaux,D.L. (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102, 43-53. Cerca con Google

41. Elz J.S. and Nayler W.G. (1988) Calcium gain during postischemic reperfusion. The effect of 2,4-dinitrophenol. Am J Pathol 131, 137–145. Cerca con Google

42. Eriksson,O., Fontaine,E., and Bernardi,P. (1998). Chemical modification of arginines by 2,3-butanedione and phenylglyoxal causes closure of the mitochondrial permeability transition pore. J. Biol. Chem. 273, 12669-12674. Cerca con Google

43. Fontaine E., Eriksson O., Ichas F. and Bernardi P. (1998) Regulation of the permeability transition pore in skeletal muscle mitochondria. Modulation by electron flow through the respiratory chain complex I. J Biol Chem 273, 12662–12668. Cerca con Google

44. Forte M., Gold B.G., Marracci G., Chaudhary P., Basso E., Johnsen D., Yu X., Fowlkes J., 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. May 1;104(18):7558-63 Cerca con Google

45. Frey T.G. and Mannella C.A.. The internal structure of mitochondria. Trends Biochem Sci. 2000 Jul;25(7):319-24. Cerca con Google

46. Ganote C.E., Worstell J. and Kaltenbach J.P. (1976) Oxygen-induced enzyme release after irreversible myocardial injury. Effects of cyanide in perfused rat hearts.Am J Pathol 84, 327–350. Cerca con Google

47. Griffiths E.J. and Halestrap A.P. (1993) Protection by Cyclosporin A of ischemia / reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol 25,1461–1469. Cerca con Google

48. Griffiths E.J. and Halestrap A.P. (1995) Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J 307, Cerca con Google

49. Gincel D. and Shoshan-Barmatz V. (2004) Glutamate interacts with VDAC and modulates opening of the mitochondrial permeability transition pore. J Bioenerg Biomembr 36, 179–186. Cerca con Google

50. Giorgio M., Migliaccio E., Orsini F., Paolucci D., Moroni M., Contursi C., Pelliccia G., Luzi L., Minucci S., Marcaccio M. et al. (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122, 221–233. Cerca con Google

51. Halestrap A.P. and Brenner C. (2003) The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem 10, 1507–1525. Cerca con Google

52. Halestrap A.P., Kerr P.M., Javadov S. and Woodfield K.Y. (1998) Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury. Biochim Biophys Acta 1366,79–94. Cerca con Google

53. Haworth,R.A. and Hunter,D.R. (1979). The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch. Biochem. Biophys. 195, 460-467. Cerca con Google

54. He L. and Lemasters J.J. (2002) Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function? FEBS Lett 512, 1–7. Cerca con Google

55. Hirsch T., Decaudin D., Susin S.A., Marchetti P., Larochette N., Resche- Rigon M. and 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, 426–434. Cerca con Google

56. Hunter,D.R. and Haworth,R.A. (1979b). The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms. Arch. Biochem. Biophys. 195, 453-459. Cerca con Google

57. Hunter,D.R. and Haworth,R.A. (1979a). The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release. Arch. Biochem. Biophys. 195, 468-477. Cerca con Google

58. Irwin W.A., Bergamin N., Sabatelli P., Reggiani C., Megighian A., Merlini L., Braghetta P., Columbaro M., Volpin D., Bressan G.M. et al. (2003) Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nat Genet 35, 267–271. Cerca con Google

59. Jennings R.B. and Ganote C.E. (1976) Mitochondrial structure and function in acute myocardial ischemic injury. Circ Res 38, I80–I91. Cerca con Google

60. Jobsis G.J., Keizers H., Vreijling J.P., de Visser M., Speer M.C., Wolterman R.A., Baas F. and Bolhuis P.A. (1996) Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures. Nat Genet 14, 113–115. Cerca con Google

61. Johans M., Milanesi E., Franck M., Johans C., Liobikas J., Panagiotaki M., Greci L., Principato G., Kinnunen P.K.J., Bernardi P. et al. (2005) Modification of permeability transition pore arginine(s) by phenylglyoxal derivatives in isolated mitochondria and mammalian cells: structure–function relationship of arginine ligands. J Biol Chem 280, 12130–12136. Cerca con Google

62. Karlsson J., Fong K.S., Hansson M.J., Elmer E., Csiszar K. and Keep M.F. (2004) Life span extension and reduced neuronal death after weekly intraventricular cyclosporin injections in the G93A transgenic mouse model of amyotrophic lateral sclerosis. J Neurosurg 101, 128–137. Cerca con Google

63. Keep M., Emer E., Fong K.S.K. and Csiszar K. (2001) Intrathecal cyclosporin prolongs survival of late-stage ALS mice. Brain Res 894, 327–331. Cerca con Google

64. Kinnally,K.W., Campo,M.L., and Tedeschi,H. (1989). Mitochondrial channel activity studied by patch-clamping mitoplasts. J. Bioenerg. Biomembr. 21, 497-506. Cerca con Google

65. Klohn P.C. Bitsch A. and Neumann H.G. (1998) Mitochondrial permeability transition is altered in early stages of carcinogenesis of 2 - acetylaminofluorene. Carcinogenesis 19, 1185–1190. Cerca con Google

66. Klohn P.C., Soriano M.E., Irwin W., Penzo D., Scorrano L., Bitsch A., Neumann H.G. and Bernardi P. (2003) Early resistance to cell death and to onset of the mitochondrial permeability transition during hepatocarcinogenesis with 2-acetylaminofluorene. Proc Natl Acad Sci USA 100, 10014–10019. Cerca con Google

67. Kokoszka J.E., Waymire K.G., Levy S.E., Sligh J.E., Cai J., Jones D.P., MacGregor G.R. and Wallace D.C. (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427, 461– 465. Cerca con Google

68. Kowaltowski A.J., Castilho R.F. and Vercesi A.E. (2001) Mitochondrial permeability transition and oxidative stress. FEBS Lett 495, 12–15. Cerca con Google

69. Krammer P.H.. CD95's deadly mission in the immune system. Nature. 2000 Oct 12;407(6805):789-95. Cerca con Google

70. Krauskopf A., Eriksson O., Craigen W.J., Forte M.A., Bernardi P.. Properties of the permeability transition in VDAC1(-/-) mitochondria. Biochim Biophysic.Acta. 2006 May-Jun;1757(5-6):590-5. Cerca con Google

71. Kroemer G., Reed J.C.. Mitochondrial control of cell death. Nat Med. 2000 May;6(5):513-519. Cerca con Google

72. Kudin A.P., Debska-Vielhaber G., Vielhaber S., Elger C.E. and Kunz W.S. (2004) The mechanism of neuroprotection by topiramate in an animal model of epilepsy. Epilepsia 45, 1478–1487. Cerca con Google

73. Le Fur G., Perrier M.L., Vaucher N., Imbault F., Flamier A., Benavides J., Uzan A., Renault C., Dubroeucq M.C. and Gueremy C. (1983) Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)- N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide.I. In vitro studies. Life Sci 32, 1839–1847. Cerca con Google

74. Leist M., Nicotera P.. The shape of cell death.Biochem Biophys Res Commun. 1997 Jul 9;236(1):1-9. Cerca con Google

75. Le Quoc K. and Le Quoc D. (1985) Crucial role of sulfhydryl groups in the mitochondrial inner membrane structure. J Biol Chem 260, 7422–7428. Cerca con Google

76. Linder M.D., Morkunaite-Haimi S., Kinnunen P.K.J., Bernardi P. and Eriksson O. (2002) Ligand-selective modulation of the permeability transition pore by arginine modification. Opposing effects of p-hydroxyphenylglyoxal and phenylglyoxal. J Biol Chem 277, 937–942. Cerca con Google

77. Liu,X., Kim,C.N., Yang,J., Jemmerson,R., and Wang,X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157. Cerca con Google

78. Majewski N., Nogueira V., Bhaskar P., Coy P.E., Skeen J.E., Gottlob K., Chandel N.S., Thompson C.B., Robey R.B. and Hay N. (2004) Hexokinase– mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell 16, 819–830. Cerca con Google

79. Massari,S. and Azzone,G.F. (1972). The equivalent pore radius of intact and damaged mitochondria and the mechanism of active shrinkage. Biochim. Biophys. Acta 283, 23-29. Cerca con Google

80. McEnery M.W., Snowman A.M., Trifiletti R.R. and Snyder S.H. (1992) Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. Proc Natl Acad Sci USA 89, 3170–3174. Cerca con Google

81. Nagata S. Apoptosis by death factor. Cell. 1997 Feb 7;88(3):355-65. Cerca con Google

82. Nakagawa T., Shimizu S., Watanabe T., Yamaguchi O., Otsu K., Yamagata H., Inohara H., Kubo T. and Tsujimoto Y. (2005) Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434, 652–658. Cerca con Google

83. Nazareth W., Yafei N. and Crompton M. (1991) Inhibition of anoxia-induced injury in heart myocytes by cyclosporin A. J Mol Cell Cardiol 23, 1351–1354. Cerca con Google

84. Neumann H.G., Ambs S. and Bitsch A. (1994) The role of nongenotoxic mechanisms in arylamine carcinogenesis. Environ Health Perspect 102 (Suppl. 6), 173–176. Cerca con Google

85. Nicolli,A., Basso,E., Petronilli,V., Wenger,R.M., and Bernardi,P. (1996). Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, a cyclosporin A-sensitive channel. J. Biol. Chem. 271, 2185-2192. Cerca con Google

86. Nicolli,A., Petronilli,V., and Bernardi,P. (1993). Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by matrix pH. Evidence that the pore open-closed probability is regulated by reversible histidine protonation. Biochemistry 32, 4461-4465. Cerca con Google

87. Papadopoulos V., Amri H., Boujrad N., Cascio C., Culty M., Garnier M., Hardwick M., Li H., Vidic B., Brown A.S. et al. (1997) Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis. Steroids 62, 21–28. Cerca con Google

88. Parker M.A., Bazan H.E., Marcheselli V., Rodriguez de Turco E.B. and Bazan N.G. (2002) Platelet-activating factor induces permeability transition and cytochrome c release in isolated brain mitochondria. J Neurosci Res 69, 39–50. Cerca con Google

89. Pastorino J.G., Shulga N. and Hoek J.B. (2002) Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem 277, 7610–7618. Cerca con Google

90. Pastorino J.G., Hoek J.B. and 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, 10545–10554. Cerca con Google

91. Pastorino J.G. and Hoek J.B. (2003) Hexokinase II: the integration of energy metabolism and control of apoptosis. Curr Med Chem 10, 1535–1551. Cerca con Google

92. Penzo D., Petronilli V., Angelin A., Cusan C., Colonna R., Scorrano L., Pagano F., Prato M., Di Lisa F. and Bernardi P. (2004) Arachidonic acid released by phospholipase A2 activation triggers Ca2+-dependent apoptosis through the mitochondrial pathway. J Biol Chem 279, 25219–25225. Cerca con Google

93. Petronilli,V., Szabo,I., and Zoratti,M. (1989). The inner mitochondrial membrane contains ion-conducting channels similar to those found in bacteria. FEBS Lett. 259, 137-143. Cerca con Google

94. Petronilli,V., Nicolli,A., Costantini,P., Colonna,R., and Bernardi,P. (1994). Regulation of the permeability transition pore, a voltage- dependent mitochondrial channel inhibited by cyclosporin A. Biochim. Biophys. Acta 1187, 255-259. Cerca con Google

95. Petronilli V., Cola C., Massari S., Colonna R. and Bernardi P. (1993) Physiological effectors modify voltage sensing by the cyclosporin A-sensitive permeability transition pore of mitochondria. J Biol Chem 268, 21939–21945. Cerca con Google

96. Petronilli,V., Cola,C., and Bernardi,P. (1993b). Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore. II. The minimal requirements for pore induction underscore a key role for transmembrane electrical potential, matrix pH, and matrix Ca2+. J. Biol. Chem. 268, 1011-1016. Cerca con Google

97. Petronilli,V., Cola,C., Massari,S., Colonna,R., and Bernardi,P. (1993a). Physiological effectors modify voltage sensing by the cyclosporin A-sensitive permeability transition pore of mitochondria. J. Biol. Chem. 268, 21939- 21945. Cerca con Google

98. Pfeiffer,D.R., Schmid,P.C., Beatrice,M.C., and Schmid,H.H. (1979). Intramitochondrial phospholipase activity and the effects of Ca2+ plus Nethylmaleimide on mitochondrial function. J. Biol. Chem. 254, 11485-11494. Cerca con Google

99. Plin C., Haddad P.S., Tillement J.P., Elimadi A. and Morin D. (2004) Protection by cyclosporin A of mitochondrial and cellular functions during a cold preservation-warm reperfusion of rat liver. Eur J Pharmacol 495, 111– 118. Cerca con Google

100. Ricchelli F., Dabbeni-Sala F., Petronilli V., Bernardi P., Hopkins B., Bova S. Species-specific modulation of the mitochondrial permeability transition by norbormide. Biochim Biophys Acta. 2005 Jun 30;1708(2):178-86. Cerca con Google

101. Sampson M.J., Decker W.K., Beaudet A.L., Ruitenbeek W., Armstrong D., Hicks M.J. and Craigen W.J. (2001) Immotile sperm and infertility in mice lacking mitochondrial voltage-dependent anion channel type 3. J Biol Chem 276, 39206–39212. Cerca con Google

102. Schinzel A.C., Takeuchi O., Huang Z., Fisher J.K., Zhou Z., Rubens J., Hetz C., Danial N.N., Moskowitz M.A. and Korsmeyer S.J. (2005) Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci USA 102, 12005– 12010. Cerca con Google

103. Schultheiss H.P. and Klingenberg M. (1984) Immunochemical characterization of the adenine nucleotide translocator. Organ specificity and conformation specificity. Eur J Biochem 143, 599–605. Cerca con Google

104. Scorrano,L., Petronilli,V., and Bernardi,P. (1997). On the voltage dependence of the mitochondrial permeability transition pore. A critical appraisal. J. Biol. Chem. 272, 12295-12299. Cerca con Google

105. Scorrano L., Penzo D., Petronilli V., Pagano F. and Bernardi P. (2001) Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-? apoptotic signaling. J Biol Chem 276, 12035–12040. Cerca con Google

106. Scorrano L., Ashiya M., Buttle K., Weiler S., Oakes S.A., Mannella C.A. and Korsmeyer S.J. (2002) A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2, 55–67. Cerca con Google

107. Siegmund B., Klietz T., Schwartz P. and Piper H.M. (1991) Temporary contractile blockade prevents hypercontracture in anoxic-reoxygenated cardiomyocytes. Am J Physiol 260, H426–H435. Cerca con Google

108. Sorgato M.C., Keller B.U. and Stuhmer W. (1987) Patchclamping of the inner mitochondrial membrane reveals a voltage-dependent ion channel. Nature 330, 498–500. Cerca con Google

109. Soriano M.E., Nicolosi L. and Bernardi P. (2004) Desensitization of the permeability transition pore by cyclosporin A prevents activation of the mitochondrial apoptotic pathway and liver damage by tumor necrosis factor-alpha. J Biol Chem 279, 36803–36808. Cerca con Google

110. Stavrovskaya I.G., Narayanan M.V., Zhang W., Krasnikov B.F., Heemskerk J., Young S.S., Blass J.P., Brown A.M., Beal M.F., Friedlander R.M. et al. (2004) Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathology. J Exp Med 200, 211–222. Cerca con Google

111. Susin,S.A., Lorenzo,H.K., Zamzami,N., Marzo,I., Snow,B.E., Brothers,G.M., Mangion,J., Jacotot,E., Costantini,P., Loeffler,M., Larochette,N., Goodlett,D.R., Aebersold,R., Siderovski,D.P., Penninger,J.M., and Kroemer,G. (1999). Molecular characterization of mitochondrial apoptosisinducing factor. Nature 397, 441-446. Cerca con Google

112. Szabo´ I., Bernardi P. and Zoratti M. (1992) Modulation of the mitochondrial megachannel by divalent cations and protons. J Biol Chem 267, 2940–2946. Cerca con Google

113. Szabo,I. and Zoratti,M. (1992). The mitochondrial megachannel is the permeability transition pore. J. Bioenerg. Biomembr. 24 , 111-117. Cerca con Google

114. Szabo,I. and Zoratti,M. (1991). The giant channel of the inner mitochondrial membrane is inhibited by cyclosporin A. J. Biol. Chem. 266, 3376-3379. Cerca con Google

115. Szabo´ I., De Pinto V. and Zoratti M. (1993) The mitochondrial permeability transition pore may comprise VDAC molecules. II. The electrophysiological properties of VDAC are compatible with those of the mitochondrial megachannel. FEBS Lett 330, 206–210. Cerca con Google

116. Szabo´ I. and Zoratti M. (1993) The mitochondrial permeability transition pore may comprise VDAC molecules. I. Binary structure and voltage dependence of the pore. FEBS Lett 330, 201–205. Cerca con Google

117. Trinei M., Giorgio M., Cicalese A., Barozzi S., Ventura A., Migliaccio E., Milia E., Padura I.M., Raker V.A., Maccarana M. et al. (2002) A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidationdamaged DNA and oxidative stress-induced apoptosis. Oncogene 21, 3872– 3878. Cerca con Google

118. Vandenabeele P., Orrenius S., Zhivotovsky B. Serine proteases and calpains fulfill important supporting roles in the apoptotic tragedy of the cellular opera. Cell Death Differ. 2005 Sep;12(9):1219-24. Cerca con Google

119. Vinogradov,A., Scarpa,A., and Chance,B. (1972). Calcium and pyridine nucleotide interaction in mitochondrial membranes. Arch. Biochem. Biophys. 152, 646-654. Cerca con Google

120. Walter L., Miyoshi H., Leverve X., Bernardi P. and Fontaine E. (2002) Regulation of the mitochondrial permeability transition pore by ubiquinone analogs. A progress report. Free Radic Res 36, 405–412. Cerca con Google

121. Wrogemann K. and Pena S.D. (1976) Mitochondrial calcium overload: a general mechanism for cell-necrosis in muscle diseases. Lancet 1, 672–674. Cerca con Google

122. Wu S., Sampson M.J., Decker W.K., Craigen W.J. Each mammalian mitochondrial outer membrane porin protein is dispensable: effects on cellular respiration. Biochim Biophys Acta. 1999 Oct 13;1452(1):68-78. Cerca con Google

123. Zamzami N. and Kroemer G. (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2, 67–71. Cerca con Google

124. Zhu S., Stavrovskaya I.G., Drozda M., Kim B.Y., Ona V., Li M., Sarang S., Liu A.S., Hartley D.M., Wufid C. et al. (2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417, 74–78. Cerca con Google

125. Zizi M., Forte M., Blachly Dyson E. and Colombini M. (1994) NADH regulates the gating of VDAC, the mitochondrial outer membrane channel. J Biol Chem 269, 1614–1616. Cerca con Google

126. Zulian A., Petronilli V., Bova S., Dabbeni-Sala F., Cargnelli G., Cavalli M., Rennison D., Stäb J., Laita O., Lee D.J., Brimble M.A., Hopkins B., Bernardi P., Ricchelli F. Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide. Biochim Biophys Acta. 2007 Jul;1767(7):980-8. Cerca con Google

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