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Mitochondrial fission and fusion and their roles in the heart

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Abstract

Mitochondria are dynamic organelles that usually exist in extensive and interconnected networks that undergo constant remodeling through fission and fusion. These processes are governed by distinct sets of proteins whose mechanism and regulation we are only beginning to fully understand. Early studies on mitochondrial dynamics were performed in yeast and simple mammalian cell culture models that allowed easy visualization of these intricate networks. Equipped with this core understanding, the field is now expanding into more complex systems. Cardiac cells are a particularly interesting example because they have unique energetic and spatial demands that make the study of their mitochondria both challenging and potentially very fruitful. This review will provide an overview of mitochondrial fission and fusion as well as recent developments in the understanding of these processes in the heart.

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References

  1. Goodpasture EW (1918) Observations on mitochondria of tumors. J Med Res 38:213–224, 211

    CAS  PubMed  Google Scholar 

  2. Lewis MR, Lewis WH (1914) Mitochondria in tissue culture. Science 39:330–333

    Article  CAS  PubMed  Google Scholar 

  3. Lewis MR, Lewis WH (1915) Mitochondria (and other cytoplasmic structures) in tissue cultures. Am J Anat 17(3):245–401, 339–401

    Article  Google Scholar 

  4. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160:189–200

    Article  CAS  PubMed  Google Scholar 

  5. Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Otera H, Nakanishi Y, Nonaka I, Goto Y, Taguchi N, Morinaga H, Maeda M, Takayanagi R, Yokota S, Mihara K (2009) Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat Cell Biol 11:958–966

    Article  CAS  PubMed  Google Scholar 

  6. Nunnari J, Marshall WF, Straight A, Murray A, Sedat JW, Walter P (1997) Mitochondrial transmission during mating in Saccharomyces cerevisiae is determined by mitochondrial fusion and fission and the intramitochondrial segregation of mitochondrial DNA. Mol Biol Cell 8:1233–1242

    CAS  PubMed  Google Scholar 

  7. Margineantu DH, Gregory Cox W, Sundell L, Sherwood SW, Beechem JM, Capaldi RA (2002) Cell cycle dependent morphology changes and associated mitochondrial DNA redistribution in mitochondria of human cell lines. Mitochondrion 1:425–435

    Article  CAS  PubMed  Google Scholar 

  8. Herlan M, Vogel F, Bornhovd C, Neupert W, Reichert AS (2003) Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J Biol Chem 278:27781–27788

    Article  CAS  PubMed  Google Scholar 

  9. Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, McCaffery JM, Chan DC (2010) Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141:280–289

    Article  CAS  PubMed  Google Scholar 

  10. Hermann GJ, Thatcher JW, Mills JP, Hales KG, Fuller MT, Nunnari J, Shaw JM (1998) Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J Cell Biol 143:359–373

    Article  CAS  PubMed  Google Scholar 

  11. Jones BA, Fangman WL (1992) Mitochondrial DNA maintenance in yeast requires a protein containing a region related to the GTP-binding domain of dynamin. Genes Dev 6:380–389

    Article  CAS  PubMed  Google Scholar 

  12. Detmer SA, Chan DC (2007) Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8:870–879

    Article  CAS  PubMed  Google Scholar 

  13. Tatsuta T, Langer T (2008) Quality control of mitochondria: protection against neurodegeneration and ageing. EMBO J 27:306–314

    Article  CAS  PubMed  Google Scholar 

  14. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433–446

    Article  CAS  PubMed  Google Scholar 

  15. Yarosh W, Monserrate J, Tong JJ, Tse S, Le PK, Nguyen K, Brachmann CB, Wallace DC, Huang T (2008) The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet 4:e6

    Article  PubMed  Google Scholar 

  16. Tang S, Le PK, Tse S, Wallace DC, Huang T (2009) Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production. PLoS ONE 4:e4492

    Article  PubMed  Google Scholar 

  17. Meeusen S, McCaffery JM, Nunnari J (2004) Mitochondrial fusion intermediates revealed in vitro. Science 305:1747–1752

    Article  CAS  PubMed  Google Scholar 

  18. Legros F, Lombes A, Frachon P, Rojo M (2002) Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol Biol Cell 13:4343–4354

    Article  CAS  PubMed  Google Scholar 

  19. Hales KG, Fuller MT (1997) Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 90:121–129

    Article  CAS  PubMed  Google Scholar 

  20. Rapaport D, Brunner M, Neupert W, Westermann B (1998) Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J Biol Chem 273:20150–20155

    Article  CAS  PubMed  Google Scholar 

  21. Santel A, Fuller MT (2001) Control of mitochondrial morphology by a human mitofusin. J Cell Sci 114:867–874

    CAS  PubMed  Google Scholar 

  22. Rojo M, Legros F, Chateau D, Lombes A (2002) Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci 115:1663–1674

    CAS  PubMed  Google Scholar 

  23. Griffin EE, Chan DC (2006) Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion. J Biol Chem 281:16599–16606

    Article  CAS  PubMed  Google Scholar 

  24. Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305:858–862

    Article  CAS  PubMed  Google Scholar 

  25. Ishihara N, Eura Y, Mihara K (2004) Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. J Cell Sci 117:6535–6546

    Article  CAS  PubMed  Google Scholar 

  26. Kuznetsov AV, Hermann M, Saks V, Hengster P, Margreiter R (2009) The cell-type specificity of mitochondrial dynamics. Int J Biochem Cell Biol 41:1928–1939

    Article  CAS  PubMed  Google Scholar 

  27. Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schroder JM, Vance JM (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot–Marie–Tooth neuropathy type 2A. Nat Genet 36:449–451

    Article  PubMed  Google Scholar 

  28. Cartoni R, Martinou JC (2009) Role of mitofusin 2 mutations in the physiopathology of Charcot–Marie–Tooth disease type 2A. Exp Neurol 218:268–273

    Article  CAS  PubMed  Google Scholar 

  29. Detmer SA, Chan DC (2007) Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J Cell Biol 176:405–414

    Article  CAS  PubMed  Google Scholar 

  30. Chen H, McCaffery JM, Chan DC (2007) Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130:548–562

    Article  CAS  PubMed  Google Scholar 

  31. Liesa M, Borda-d’Agua B, Medina-Gomez G, Lelliott CJ, Paz JC, Rojo M, Palacin M, Vidal-Puig A, Zorzano A (2008) Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta. PLoS ONE 3:e3613

    Article  PubMed  Google Scholar 

  32. Li Y, Yin R, Liu J, Wang P, Wu S, Luo J, Zhelyabovska O, Yang Q (2009) Peroxisome proliferator-activated receptor delta regulates mitofusin 2 expression in the heart. J Mol Cell Cardiol 46:876–882

    Article  CAS  PubMed  Google Scholar 

  33. Cartoni R, Leger B, Hock MB, Praz M, Crettenand A, Pich S, Ziltener JL, Luthi F, Deriaz O, Zorzano A, Gobelet C, Kralli A, Russell AP (2005) Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J Physiol 567:349–358

    Article  CAS  PubMed  Google Scholar 

  34. Ding H, Jiang N, Liu H, Liu X, Liu D, Zhao F, Wen L, Liu S, Ji LL, Zhang Y (2010) Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle. Biochim Biophys Acta 1800:250–256

    CAS  PubMed  Google Scholar 

  35. Poole AC, Thomas RE, Yu S, Vincow ES, Pallanck L (2010) The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS ONE 5:e10054

    Article  PubMed  Google Scholar 

  36. Ziviani E, Tao RN, Whitworth AJ (2010) Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci USA 107:5018–5023

    Article  CAS  PubMed  Google Scholar 

  37. Neutzner A, Youle RJ (2005) Instability of the mitofusin Fzo1 regulates mitochondrial morphology during the mating response of the yeast Saccharomyces cerevisiae. J Biol Chem 280:18598–18603

    Article  CAS  PubMed  Google Scholar 

  38. Cohen MM, Leboucher GP, Livnat-Levanon N, Glickman MH, Weissman AM (2008) Ubiquitin-proteasome-dependent degradation of a mitofusin, a critical regulator of mitochondrial fusion. Mol Biol Cell 19:2457–2464

    Article  CAS  PubMed  Google Scholar 

  39. Wong ED, Wagner JA, Gorsich SW, McCaffery JM, Shaw JM, Nunnari J (2000) The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J Cell Biol 151:341–352

    Article  CAS  PubMed  Google Scholar 

  40. Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker C, Lasquellec L, Arnaud B, Ducommun B, Kaplan J, Hamel CP (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26:207–210

    Article  CAS  PubMed  Google Scholar 

  41. Ishihara N, Fujita Y, Oka T, Mihara K (2006) Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J 25:2966–2977

    Article  CAS  PubMed  Google Scholar 

  42. Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM (2009) Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J Cell Biol 187:959–966

    Article  CAS  PubMed  Google Scholar 

  43. Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, Martinou JC, Westermann B, Rugarli EI, Langer T (2009) Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol 187:1023–1036

    Article  CAS  PubMed  Google Scholar 

  44. Song Z, Chen H, Fiket M, Alexander C, Chan DC (2007) OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol 178:749–755

    Article  CAS  PubMed  Google Scholar 

  45. McBride H, Soubannier V (2010) Mitochondrial function: OMA1 and OPA1, the grandmasters of mitochondrial health. Curr Biol 20:R274–R276

    Article  CAS  PubMed  Google Scholar 

  46. Meeusen S, DeVay R, Block J, Cassidy-Stone A, Wayson S, McCaffery JM, Nunnari J (2006) Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127:383–395

    Article  CAS  PubMed  Google Scholar 

  47. Sesaki H, Jensen RE (2001) UGO1 encodes an outer membrane protein required for mitochondrial fusion. J Cell Biol 152:1123–1134

    Article  CAS  PubMed  Google Scholar 

  48. Sesaki H, Jensen RE (2004) Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J Biol Chem 279:28298–28303

    Article  CAS  PubMed  Google Scholar 

  49. Hoppins S, Horner J, Song C, McCaffery JM, Nunnari J (2009) Mitochondrial outer and inner membrane fusion requires a modified carrier protein. J Cell Biol 184:569–581

    Article  CAS  PubMed  Google Scholar 

  50. Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26:211–215

    Article  CAS  PubMed  Google Scholar 

  51. Zanna C, Ghelli A, Porcelli AM, Karbowski M, Youle RJ, Schimpf S, Wissinger B, Pinti M, Cossarizza A, Vidoni S, Valentino ML, Rugolo M, Carelli V (2008) OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131:352–367

    Article  PubMed  Google Scholar 

  52. White KE, Davies VJ, Hogan VE, Piechota MJ, Nichols PP, Turnbull DM, Votruba M (2009) OPA1 deficiency associated with increased autophagy in retinal ganglion cells in a murine model of dominant optic atrophy. Invest Ophthalmol Vis Sci 50:2567–2571

    Article  PubMed  Google Scholar 

  53. Bleazard W, McCaffery JM, King EJ, Bale S, Mozdy A, Tieu Q, Nunnari J, Shaw JM (1999) The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1:298–304

    Article  CAS  PubMed  Google Scholar 

  54. Otsuga D, Keegan BR, Brisch E, Thatcher JW, Hermann GJ, Bleazard W, Shaw JM (1998) The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J Cell Biol 143:333–349

    Article  CAS  PubMed  Google Scholar 

  55. Smirnova E, Shurland DL, Ryazantsev SN, van der Bliek AM (1998) A human dynamin-related protein controls the distribution of mitochondria. J Cell Biol 143:351–358

    Article  CAS  PubMed  Google Scholar 

  56. Ingerman E, Perkins EM, Marino M, Mears JA, McCaffery JM, Hinshaw JE, Nunnari J (2005) Dnm1 forms spirals that are structurally tailored to fit mitochondria. J Cell Biol 170:1021–1027

    Article  CAS  PubMed  Google Scholar 

  57. Lackner LL, Horner JS, Nunnari J (2009) Mechanistic analysis of a dynamin effector. Science 325:874–877

    Article  CAS  PubMed  Google Scholar 

  58. Yoon Y, Pitts KR, McNiven MA (2001) Mammalian dynamin-like protein DLP1 tubulates membranes. Mol Biol Cell 12:2894–2905

    CAS  PubMed  Google Scholar 

  59. Mozdy AD, McCaffery JM, Shaw JM (2000) Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol 151:367–380

    Article  CAS  PubMed  Google Scholar 

  60. Jakobs S, Martini N, Schauss AC, Egner A, Westermann B, Hell SW (2003) Spatial and temporal dynamics of budding yeast mitochondria lacking the division component Fis1p. J Cell Sci 116:2005–2014

    Article  CAS  PubMed  Google Scholar 

  61. James DI, Parone PA, Mattenberger Y, Martinou JC (2003) hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem 278:36373–36379

    Article  CAS  PubMed  Google Scholar 

  62. Yoon Y, Krueger EW, Oswald BJ, McNiven MA (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 23:5409–5420

    Article  CAS  PubMed  Google Scholar 

  63. Suzuki M, Neutzner A, Tjandra N, Youle RJ (2005) Novel structure of the N terminus in yeast Fis1 correlates with a specialized function in mitochondrial fission. J Biol Chem 280:21444–21452

    Article  CAS  PubMed  Google Scholar 

  64. Suzuki M, Jeong SY, Karbowski M, Youle RJ, Tjandra N (2003) The solution structure of human mitochondria fission protein Fis1 reveals a novel TPR-like helix bundle. J Mol Biol 334:445–458

    Article  CAS  PubMed  Google Scholar 

  65. Tieu Q, Okreglak V, Naylor K, Nunnari J (2002) The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission. J Cell Biol 158:445–452

    Article  CAS  PubMed  Google Scholar 

  66. Griffin EE, Graumann J, Chan DC (2005) The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. J Cell Biol 170:237–248

    Article  CAS  PubMed  Google Scholar 

  67. Tieu Q, Nunnari J (2000) Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J Cell Biol 151:353–366

    Article  CAS  PubMed  Google Scholar 

  68. Gandre-Babbe S, van der Bliek AM (2008) The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell 19:2402–2412

    Article  CAS  PubMed  Google Scholar 

  69. Beech PL, Nheu T, Schultz T, Herbert S, Lithgow T, Gilson PR, McFadden GI (2000) Mitochondrial FtsZ in a chromophyte alga. Science 287:1276–1279

    Article  CAS  PubMed  Google Scholar 

  70. Gilson PR, Yu XC, Hereld D, Barth C, Savage A, Kiefel BR, Lay S, Fisher PR, Margolin W, Beech PL (2003) Two Dictyostelium orthologs of the prokaryotic cell division protein FtsZ localize to mitochondria and are required for the maintenance of normal mitochondrial morphology. Eukaryot Cell 2:1315–1326

    Article  CAS  PubMed  Google Scholar 

  71. Nishida K, Takahara M, Miyagishima SY, Kuroiwa H, Matsuzaki M, Kuroiwa T (2003) Dynamic recruitment of dynamin for final mitochondrial severance in a primitive red alga. Proc Natl Acad Sci USA 100:2146–2151

    Article  CAS  PubMed  Google Scholar 

  72. Hoppel CL, Tandler B, Fujioka H, Riva A (2009) Dynamic organization of mitochondria in human heart and in myocardial disease. Int J Biochem Cell Biol 41:1949–1956

    Article  CAS  PubMed  Google Scholar 

  73. Kraus B, Cain H (1980) Giant mitochondria in the human myocardium—morphogenesis and fate. Virchows Arch B Cell Pathol Incl Mol Pathol 33:77–89

    Article  CAS  PubMed  Google Scholar 

  74. Coleman R, Silbermann M, Gershon D, Reznick AZ (1987) Giant mitochondria in the myocardium of aging and endurance-trained mice. Gerontology 33:34–39

    Article  CAS  PubMed  Google Scholar 

  75. Kanzaki Y, Terasaki F, Okabe M, Otsuka K, Katashima T, Fujita S, Ito T, Kitaura Y (2010) Giant mitochondria in the myocardium of a patient with mitochondrial cardiomyopathy: transmission and 3-dimensional scanning electron microscopy. Circulation 121:831–832

    Article  PubMed  Google Scholar 

  76. Bhimji S, Godin DV, McNeill JH (1986) Isoproterenol-induced myocardial alterations in alloxan-diabetic rabbits. Can J Cardiol 2:313–319

    CAS  PubMed  Google Scholar 

  77. Yu T, Sheu SS, Robotham JL, Yoon Y (2008) Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 79:341–351

    Article  CAS  PubMed  Google Scholar 

  78. Beraud N, Pelloux S, Usson Y, Kuznetsov AV, Ronot X, Tourneur Y, Saks V (2009) Mitochondrial dynamics in heart cells: very low amplitude high frequency fluctuations in adult cardiomyocytes and flow motion in non beating Hl-1 cells. J Bioenerg Biomembr 41:195–214

    Article  CAS  PubMed  Google Scholar 

  79. Hom J, Yu T, Yoon Y, Porter G, Sheu SS (2010) Regulation of mitochondrial fission by intracellular Ca(2+) in rat ventricular myocytes. Biochim Biophys Acta 1797:913–921

    Article  CAS  PubMed  Google Scholar 

  80. Ong SB, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ (2010) Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation 121:2012–2022

    Article  CAS  PubMed  Google Scholar 

  81. Chen L, Gong Q, Stice JP, Knowlton AA (2009) Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc Res 84:91–99

    Article  CAS  PubMed  Google Scholar 

  82. Ashrafian H, Docherty L, Leo V, Towlson C, Neilan M, Steeples V, Lygate CA, Hough T, Townsend S, Williams D, Wells S, Norris D, Glyn-Jones S, Land J, Barbaric I, Lalanne Z, Denny P, Szumska D, Bhattacharya S, Griffin JL, Hargreaves I, Fernandez-Fuentes N, Cheeseman M, Watkins H, Dear TN (2010) A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy. PLoS Genet 6:e1001000

    Article  PubMed  Google Scholar 

  83. Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C, Kuwana T, Kurth MJ, Shaw JT, Hinshaw JE, Green DR, Nunnari J (2008) Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell 14:193–204

    Article  CAS  PubMed  Google Scholar 

  84. Suen DF, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22:1577–1590

    Article  CAS  PubMed  Google Scholar 

  85. Hausenloy DJ, Yellon DM (2009) Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis 204:334–341

    Article  CAS  PubMed  Google Scholar 

  86. Huffmyer J, Raphael J (2009) Physiology and pharmacology of myocardial preconditioning and postconditioning. Semin Cardiothorac Vasc Anesth 13:5–18

    Article  PubMed  Google Scholar 

  87. Murphy E, Steenbergen C (2007) Preconditioning: the mitochondrial connection. Annu Rev Physiol 69:51–67

    Article  CAS  PubMed  Google Scholar 

  88. Burwell LS, Brookes PS (2008) Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia–reperfusion injury. Antioxid Redox Signal 10:579–599

    Article  CAS  PubMed  Google Scholar 

  89. Nakamura T, Cieplak P, Cho DH, Godzik A, Lipton SA (2010) S-nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration. Mitochondrion 10:573–578

    Article  CAS  PubMed  Google Scholar 

  90. Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324:102–105

    Article  CAS  PubMed  Google Scholar 

  91. Bossy B, Petrilli A, Klinglmayr E, Chen J, Lutz-Meindl U, Knott AB, Masliah E, Schwarzenbacher R, Bossy-Wetzel E (2010) S-nitrosylation of DRP1 does not affect enzymatic activity and is not specific to Alzheimer’s disease. J Alzheimers Dis 20(Suppl 2):S513–S526

    PubMed  Google Scholar 

  92. De Palma C, Falcone S, Pisoni S, Cipolat S, Panzeri C, Pambianco S, Pisconti A, Allevi R, Bassi MT, Cossu G, Pozzan T, Moncada S, Scorrano L, Brunelli S, Clementi E (2010) Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation. Cell Death Differ. 2010 May 14. doi:10.1172/JC140373

  93. Kanazawa T, Zappaterra MD, Hasegawa A, Wright AP, Newman-Smith ED, Buttle KF, McDonald K, Mannella CA, van der Bliek AM (2008) The C. elegans Opa1 homologue EAT-3 is essential for resistance to free radicals. PLoS Genet 4:e1000022

    Article  PubMed  Google Scholar 

  94. McQuibban GA, Lee JR, Zheng L, Juusola M, Freeman M (2006) Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function. Curr Biol 16:982–989

    Article  CAS  PubMed  Google Scholar 

  95. Labrousse AM, Zappaterra MD, Rube DA, van der Bliek AM (1999) C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol Cell 4:815–826

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors’ would like to thank Geoffrey Hesketh for the images used in Fig. 2. Work in the authors’ laboratory is funded by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health.

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The authors declare no conflict of interests related to this study.

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  1. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    Lesley A. Kane & Richard J. Youle

  2. Surgical Neurology Branch, NINDS, Porter Neuroscience Research Center, Building 35, Room 2C-917 35 Convent Drive, MSC 3704, Bethesda, MD, 20892-3704, USA

    Richard J. Youle

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Kane, L.A., Youle, R.J. Mitochondrial fission and fusion and their roles in the heart. J Mol Med 88, 971–979 (2010). https://doi.org/10.1007/s00109-010-0674-6

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  • DOI: https://doi.org/10.1007/s00109-010-0674-6

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