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Mitochondrial Channels as Potential Targets for Pharmacological Strategies in Brain Ischemia

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New Strategies in Stroke Intervention

Part of the book series: Contemporary Neuroscience ((CNEURO))

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Abstract

Ischemic stroke is a major cause of death and disability urgently requiring novel therapeutic approaches. Deprivation of oxygen and respiratory substrate during an ischemic episode has its most immediate impact on mitochondria, the body’s primary oxygen consumers. Mitochondrial function is in turn critically dependent on a range of carriers and channels, most of which remain inadequately understood at the genetic and molecular level. As mitochondrial channels are involved in energy production, calcium handling, generation of reactive oxygen species (ROS) and cell-death related signaling, it is evident that increased understanding of these processes and their regulation will help the search for novel rational approaches to therapy.

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References

  1. O’Rourke B. Evidence for mitochondrial K+ channels and their role in cardioprotection. Circ Res 94: 420, 2004.

    Article  PubMed  Google Scholar 

  2. Grover GJ and Garlid KD. ATP-Sensitive potassium channels: a review of their cardioprotective pharmacology. J Mol Cell Cardiol 32: 677, 2000.

    Article  PubMed  CAS  Google Scholar 

  3. Inoue I, Nagase H, Kishi K, and Higuti T. ATP-sensitive K+ channel in the mitochondrial inner membrane. Nature 352: 244, 1991.

    Article  PubMed  CAS  Google Scholar 

  4. Aguilar-Bryan L and Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev 20: 101, 1999.

    Article  PubMed  CAS  Google Scholar 

  5. Lacza Z, Snipes JA, Kis B, Szabo C, Grover G, and Busija DW. Investigation of the subunit composition and the pharmacology of the mitochondrial ATP-dependent K+ channel in the brain. Brain Res 994: 27, 2003.

    Article  PubMed  CAS  Google Scholar 

  6. Foster DB, Rucker JJ, and Marban E. Is Kir6.1 a subunit of mitoK(ATP)? Biochem Biophys Res Commun 366: 649, 2008.

    Article  PubMed  CAS  Google Scholar 

  7. Suzuki M, Sasaki N, Miki T, Sakamoto N, Ohmoto-Sekine Y, Tamagawa M, Seino S, Marban E, and Nakaya H. Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice. J Clin Invest 109: 509, 2002.

    PubMed  CAS  Google Scholar 

  8. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, and Warden CH. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15: 269, 1997.

    Article  PubMed  CAS  Google Scholar 

  9. Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Dulloo A, Seydoux J, Muzzin P, and Giacobino JP. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 408: 39, 1997.

    Article  PubMed  CAS  Google Scholar 

  10. Mao W, Yu XX, Zhong A, Li W, Brush J, Sherwood SW, Adams SH, and Pan G. UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett 443: 326, 1999.

    Article  PubMed  CAS  Google Scholar 

  11. Sanchis D, Fleury C, Chomiki N, Goubern M, Huang Q, Neverova M, Gregoire F, Easlick J, Raimbault S, Levi-Meyrueis C, Miroux B, Collins S, Seldin M, Richard D, Warden C, Bouillaud F, and Ricquier D. BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast. J Biol Chem 273: 34611, 1998.

    Article  PubMed  CAS  Google Scholar 

  12. Pecqueur C, Cassard-Doulcier AM, Raimbault S, Miroux B, Fleury C, Gelly C, Bouillaud F, and Ricquier D. Functional organization of the human uncoupling protein-2 gene, and juxtaposition to the uncoupling protein-3 gene. Biochem Biophys Res Commun 255: 40, 1999.

    Article  PubMed  CAS  Google Scholar 

  13. Bouillaud F, Couplan E, Pecqueur C, and Ricquier D. Homologues of the uncoupling protein from brown adipose tissue (UCP1): UCP2, UCP3, BMCP1 and UCP4. Biochim Biophys Acta 1504: 107, 2001.

    Article  PubMed  CAS  Google Scholar 

  14. Hunter DR and Haworth RA. The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms. Arch Biochem Biophys 195: 453, 1979.

    Article  PubMed  CAS  Google Scholar 

  15. Hunter DR and Haworth RA. The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release. Arch Biochem Biophys 195: 468, 1979.

    Article  PubMed  CAS  Google Scholar 

  16. Haworth RA and Hunter DR. The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch Biochem Biophys 195: 460, 1979.

    Article  PubMed  CAS  Google Scholar 

  17. Zoratti M, Szabo I, and De Marchi U. Mitochondrial permeability transitions: how many doors to the house? Biochim Biophys Acta 1706: 40, 2005.

    Google Scholar 

  18. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, and Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434: 658, 2005.

    Article  PubMed  CAS  Google Scholar 

  19. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, and Molkentin JD. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9: 550, 2007.

    Article  PubMed  CAS  Google Scholar 

  20. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, and Wallace DC. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427: 461, 2004.

    Article  PubMed  CAS  Google Scholar 

  21. Bowles KR, Zintz C, Abraham SE, Brandon L, Bowles NE, and Towbin JA. Genomic characterization of the human peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor gene: assessment of its role in familial dilated cardiomyopathy. Hum Genet 105: 582, 1999.

    Article  PubMed  CAS  Google Scholar 

  22. Blachly-Dyson E, Baldini A, Litt M, McCabe ER, and Forte M. Human genes encoding the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane: mapping and identification of two new isoforms. Genomics 20: 62, 1994.

    Article  PubMed  CAS  Google Scholar 

  23. Messina A, Oliva M, Rosato C, Huizing M, Ruitenbeek W, van den Heuvel LP, Forte M, Rocchi M, and De Pinto V. Mapping of the human Voltage-Dependent Anion Channel isoforms 1 and 2 reconsidered. Biochem Biophys Res Commun 255: 707, 1999.

    Article  PubMed  CAS  Google Scholar 

  24. McEnery MW, Snowman AM, Trifiletti RR, and Snyder SH. 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, 1992.

    Article  PubMed  CAS  Google Scholar 

  25. Azarashvili T, Grachev D, Krestinina O, Evtodienko Y, Yurkov I, Papadopoulos V, and Reiser G. The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Cell Calcium 42: 27, 2007.

    Article  PubMed  CAS  Google Scholar 

  26. Leung AW and Halestrap AP. Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore. Biochim Biophys Acta 1777: 946, 2008.

    Article  PubMed  CAS  Google Scholar 

  27. Zhou M, Tanaka O, Sekiguchi M, Sakabe K, Anzai M, Izumida I, Inoue T, Kawahara K, and Abe H. Localization of the ATP-sensitive potassium channel subunit (Kir6. 1/uK(ATP)-1) in rat brain. Brain Res Mol Brain Res 74: 15, 1999.

    Article  PubMed  CAS  Google Scholar 

  28. de Bilbao F, Arsenijevic D, Vallet P, Hjelle OP, Ottersen OP, Bouras C, Raffin Y, Abou K, Langhans W, Collins S, Plamondon J, ves-Guerra MC, Haguenauer A, Garcia I, Richard D, Ricquier D, and Giannakopoulos P. Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels. J Neurochem 89: 1283, 2004.

    Article  PubMed  CAS  Google Scholar 

  29. Brustovetsky N, Brustovetsky T, Purl KJ, Capano M, Crompton M, and Dubinsky JM. Increased susceptibility of striatal mitochondria to calcium-induced permeability transition. J Neuropsychiatry 23: 4858, 2003.

    CAS  Google Scholar 

  30. Cesar MC and Wilson JE. All three isoforms of the voltage-dependent anion channel (VDAC1, VDAC2, and VDAC3) are present in mitochondria from bovine, rabbit, and rat brain. Arch Biochem Biophys 422: 191, 2004.

    Article  CAS  Google Scholar 

  31. Doerner A, Pauschinger M, Badorff A, Noutsias M, Giessen S, Schulze K, Bilger J, Rauch U, and Schultheiss HP. Tissue-specific transcription pattern of the adenine nucleotide translocase isoforms in humans. FEBS Lett 414: 258, 1997.

    Article  PubMed  CAS  Google Scholar 

  32. Mironova GD, Skarga YY, Grigoriev SM, Negoda AE, Kolomytkin OV, and Marinov BS. Reconstitution of the mitochondrial ATP-dependent potassium channel into bilayer lipid membrane. J Bioenerg Biomembr 31: 159, 1999.

    Article  PubMed  CAS  Google Scholar 

  33. Fornazari M, de Paula JG, Castilho RF, and Kowaltowski AJ. Redox properties of the adenoside triphosphate-sensitive K+ channel in brain mitochondria. J Neurosci Nurs 86: 1548, 2008.

    CAS  Google Scholar 

  34. Loupatatzis C, Seitz G, Schonfeld P, Lang F, and Siemen D. Single-channel currents of the permeability transition pore from the inner mitochondrial membrane of rat liver and of a human hepatoma cell line. Cell Physiol Biochem 12: 269, 2002.

    Article  PubMed  CAS  Google Scholar 

  35. Campello S, De Marchi U, Szabo I, Tombola F, Martinou JC, and Zoratti M. The properties of the mitochondrial megachannel in mitoplasts from human colon carcinoma cells are not influenced by Bax. FEBS Lett 579: 3695, 2005.

    Article  PubMed  CAS  Google Scholar 

  36. De Marchi U, Basso E, Szabo I, and Zoratti M. Electrophysiological characterization of the Cyclophilin D-deleted mitochondrial permeability transition pore. Mol Membr Biol 23: 521, 2006.

    Article  PubMed  CAS  Google Scholar 

  37. Garlid KD and Paucek P. Mitochondrial potassium transport: the K(+) cycle. Biochim Biophys Acta 1606: 23, 2003.

    Article  PubMed  CAS  Google Scholar 

  38. Echtay KS. Mitochondrial uncoupling proteins – what is their physiological role? Free Radic Biol Med 43: 1351, 2007.

    Article  PubMed  CAS  Google Scholar 

  39. Criscuolo F, Mozo J, Hurtaud C, Nubel T, and Bouillaud F. UCP2, UCP3, avUCP, what do they do when proton transport is not stimulated? Possible relevance to pyruvate and glutamine metabolism. Biochim Biophys Acta 1757: 1284, 2006.

    Article  PubMed  CAS  Google Scholar 

  40. Trenker M, Malli R, Fertschai I, Levak-Frank S, and Graier WF. Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport. Nat Cell Biol 9: 445, 2007.

    Article  PubMed  CAS  Google Scholar 

  41. Murchison D and Griffith WH. Mitochondria buffer non-toxic calcium loads and release calcium through the mitochondrial permeability transition pore and sodium/calcium exchanger in rat basal forebrain neurons. Brain Res 854: 139, 2000.

    Article  PubMed  CAS  Google Scholar 

  42. Papadopoulos V. In search of the function of the peripheral-type benzodiazepine receptor. Endocr Res 30: 677, 2004.

    Article  PubMed  CAS  Google Scholar 

  43. Grover GJ, McCullough JR, Henry DE, Conder ML, and Sleph PG. Anti-ischemic effects of the potassium channel activators pinacidil and cromakalim and the reversal of these effects with the potassium channel blocker glyburide. J Pharmacol Exp Ther 251: 98, 1989.

    PubMed  CAS  Google Scholar 

  44. Gross GJ and Auchampach JA. Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res 70: 223, 1992.

    PubMed  CAS  Google Scholar 

  45. Ljubkovic M, Marinovic J, Fuchs A, Bosnjak ZJ, and Bienengraeber M. Targeted expression of Kir6.2 in mitochondria confers protection against hypoxic stress. J Physiol 577: 17, 2006.

    Article  PubMed  CAS  Google Scholar 

  46. Bajgar R, Seetharaman S, Kowaltowski AJ, Garlid KD, and Paucek P. Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain. J Biol Chem 276: 33369, 2001.

    Article  PubMed  CAS  Google Scholar 

  47. Lauritzen I, De Weille JR, and Lazdunski M. The potassium channel opener (–)-cromakalim prevents glutamate-induced cell death in hippocampal neurons. J Neurochem 69: 1570, 1997.

    Article  PubMed  CAS  Google Scholar 

  48. Mayanagi K, Gaspar T, Katakam PV, Kis B, and Busija DW. The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 27: 348, 2007.

    Article  PubMed  CAS  Google Scholar 

  49. Nistico R, Piccirilli S, Sebastianelli L, Nistico G, Bernardi G, and Mercuri NB. The blockade of K(+)-ATP channels has neuroprotective effects in an in vitro model of brain ischemia, Int. Rev Neurobiol 82: 383, 2007.

    Article  CAS  Google Scholar 

  50. Liu D, Slevin JR, Lu C, Chan SL, Hansson M, Elmer E, and Mattson MP. Involvement of mitochondrial K+ release and cellular efflux in ischemic and apoptotic neuronal death. J Neurochem 86: 966, 2003.

    Article  PubMed  CAS  Google Scholar 

  51. Andrukhiv A, Costa AD, West IC, and Garlid KD. Opening mitoKATP increases superoxide generation from complex I of the electron transport chain. Am J Physiol Heart Circ Physiol 291: H2067–H2074, 2006.

    Article  PubMed  CAS  Google Scholar 

  52. Facundo HT, Carreira RS, de Paula JG, Santos CC, Ferranti R, Laurindo FR, and Kowaltowski AJ. Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity. Free Radic Biol Med 40: 469, 2006.

    Article  PubMed  CAS  Google Scholar 

  53. Minners J, Lacerda L, Yellon DM, Opie LH, McLeod CJ, and Sack MN. Diazoxide-induced respiratory inhibition – a putative mitochondrial K(ATP) channel independent mechanism of pharmacological preconditioning. Mol Cell Biochem 294: 11, 2007.

    Article  PubMed  CAS  Google Scholar 

  54. Gaspar T, Snipes JA, Busija AR, Kis B, Domoki F, Bari F, and Busija DW. ROS-independent preconditioning in neurons via activation of mitoK(ATP) channels by BMS-191095. J Cereb Blood Flow Metab 28: 1090, 2008.

    Article  PubMed  CAS  Google Scholar 

  55. Garlid KD, Dos SP, Xie ZJ, Costa AD, and Paucek P. Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K(+) channel in cardiac function and cardioprotection. Biochim Biophys Acta 1606: 1, 2003.

    Article  PubMed  CAS  Google Scholar 

  56. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, and Vinten-Johansen J. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285: H579–H588, 2003.

    PubMed  CAS  Google Scholar 

  57. Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L’Huillier I, Aupetit JF, Bonnefoy E, Finet G, André-Fouët X, and Ovize M. Postconditioning the human heart. Circulation 112: 2143, 2005.

    Article  PubMed  Google Scholar 

  58. Zhao H, Sapolsky RM, and Steinberg GK. Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats. J Cereb Blood Flow Metab 26: 1114, 2006.

    Article  PubMed  CAS  Google Scholar 

  59. Lee JJ, Li L, Jung HH, and Zuo Z. Postconditioning with isoflurane reduced ischemia-induced brain injury in rats. Anesthesiology 108: 1055, 2008.

    Article  PubMed  CAS  Google Scholar 

  60. Burda J, Danielisova V, Nemethova M, Gottlieb M, Matiasova M, Domorakova I, Mechirova E, Ferikova M, Salinas M, and Burda R. Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain. Cell Mol Neurobiol 26: 1141, 2006.

    Article  PubMed  Google Scholar 

  61. Nicholls DG, Johnson-Cadwell L, Vesce S, Jekabsons M, and Yadava N. Bioenergetics of mitochondria in cultured neurons and their role in glutamate excitotoxicity. J Neurosci Nurs 85: 3206, 2007.

    CAS  Google Scholar 

  62. Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, Warden CH, Castilho RF, Melcher T, Gonzalez-Zulueta M, Nikolich K, and Wieloch T. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 9: 1062, 2003.

    Article  PubMed  CAS  Google Scholar 

  63. Brennan JP, Berry RG, Baghai M, Duchen MR, and Shattock MJ. FCCP is cardioprotective at concentrations that cause mitochondrial oxidation without detectable depolarisation. Cardiovasc Res 72: 322, 2006.

    Article  PubMed  CAS  Google Scholar 

  64. Pandya JD, Pauly JR, Nukala VN, Sebastian AH, Day KM, Korde AS, Maragos WF, Hall ED, and Sullivan PG. Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents. J Neurotrauma 24: 798, 2007.

    Article  PubMed  Google Scholar 

  65. Johnson-Cadwell LI, Jekabsons MB, Wang A, Polster BM, and Nicholls DG. ‘Mild Uncoupling’ does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress. J Neurochem 101: 1619, 2007.

    Article  PubMed  CAS  Google Scholar 

  66. Tretter L and Adam-Vizi V. Uncoupling is without an effect on the production of reactive oxygen species by in situ synaptic mitochondria. J Neurochem 103: 1864, 2007.

    Article  PubMed  CAS  Google Scholar 

  67. Gomez L, Thibault H, Gharib A, Dumont JM, Vuagniaux G, Scalfaro P, Derumeaux G, and Ovize M. 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–H1661, 2007.

    Article  PubMed  CAS  Google Scholar 

  68. Wang JY, Shen J, Gao Q, Ye ZG, Yang SY, Liang HW, Bruce IC, Luo BY, and Xia Q. Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats. Stroke 39: 983, 2008.

    Article  PubMed  Google Scholar 

  69. Sharma SS and Gupta S. Neuroprotective effect of MnTMPyP, a superoxide dismutase/catalase mimetic in global cerebral ischemia is mediated through reduction of oxidative stress and DNA fragmentation. Eur J Pharmacol 561: 72, 2007.

    Article  PubMed  CAS  Google Scholar 

  70. Szeto HH. Mitochondria-targeted cytoprotective peptides for ischemia-reperfusion injury. Antioxid Redox Signal 10: 601, 2008.

    Article  PubMed  CAS  Google Scholar 

  71. Luo J, Chen H, Kintner DB, Shull GE, and Sun D. Inhibition of Na+/H+ exchanger isoform 1 attenuates mitochondrial cytochrome C release in cortical neurons following in vitro ischemia. Acta Neurochir Suppl 96: 244, 2006.

    Article  Google Scholar 

  72. Mentzer RM Jr., Bartels C, Bolli R, Boyce S, Buckberg GD, Chaitman B, Haverich A, Knight J, Menasche P, Myers ML, Nicolau J, Simoons M, Thulin L, and Weisel RD. Sodium-hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study. Ann Thorac Surg 85: 1261, 2008.

    Article  PubMed  Google Scholar 

  73. Schinzel AC, Takeuchi O, Huang Z, Fisher JK, Zhou Z, Rubens J, Hetz C, Danial NN, Moskowitz MA, and Korsmeyer SJ. 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, 2005.

    Article  PubMed  CAS  Google Scholar 

  74. Akdemir G, Ergungor MF, Sezer M, Albayrak L, Daglioglu E, and Kilinc K. Therapeutic efficacy of intraventricular cyclosporine A and methylprednisolone on a global cerebral ischemia model in rats. Neurol Res 27: 827, 2005.

    Article  PubMed  CAS  Google Scholar 

  75. Stavrovskaya IG, Narayanan MV, Zhang W, Krasnikov BF, Heemskerk J, Young SS, Blass JP, Brown AM, Beal MF, Friedlander RM, and Kristal BS. Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathology. J Exp Med 200: 211, 2004.

    Article  PubMed  CAS  Google Scholar 

  76. Zhang WH, Wang H, Wang X, Narayanan MV, Stavrovskaya IG, Kristal BS, and Friedlander RM. Nortriptyline protects mitochondria and reduces cerebral ischemia/hypoxia injury. Stroke 39: 455, 2008.

    Article  PubMed  Google Scholar 

  77. Muramatsu Y, Furuichi Y, Tojo N, Moriguchi A, Maemoto T, Nakada H, Hino M, and Matsuoka N. Neuroprotective efficacy of FR901459, a novel derivative of cyclosporin A, in in vitro mitochondrial damage and in vivo transient cerebral ischemia models. Brain Res 1149: 181, 2007.

    Article  PubMed  CAS  Google Scholar 

  78. Yamada Y, Akita H, Kogure K, Kamiya H, and Harashima H. Mitochondrial drug delivery and mitochondrial disease therapy – an approach to liposome-based delivery targeted to mitochondria. Mitochondrion 7: 63, 2007.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, University College London, Gower Street, WC1E 6BT, London, UK

    Rosemary H Milton

  2. Department of Physiology, University College London, WC1E 6BT, London, UK

    Michael R Duchen

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  1. Fac. Medicina e Chirurgia, Università di Napoli, Via Sergio Pansini 5, Napoli, 80131, Italy

    Lucio Annunziato

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Milton, R.H., Duchen, M.R. (2009). Mitochondrial Channels as Potential Targets for Pharmacological Strategies in Brain Ischemia. In: Annunziato, L. (eds) New Strategies in Stroke Intervention. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60761-280-3_3

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