1932

Abstract

Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously integrate and respond to cellular cues and demands by remodeling their morphology. These processes define mitochondrial dynamics and inextricably link the fate of the mitochondrion and that of the host eukaryote, as exemplified by the human diseases that result from mutations in mitochondrial dynamics proteins. In this review, we delineate the architecture of mitochondria and define the mechanisms by which they modify their shape. Key players in these mechanisms are discussed, along with their role in manipulating mitochondrial morphology during cellular action and development. Throughout, we highlight the evolutionary context in which mitochondrial dynamics emerged and consider unanswered questions whose dissection might lead to mitochondrial morphology–based therapies.

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2016-02-10
2024-03-29
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Literature Cited

  1. Benson DR, Rivera M. 1.  2013. Heme uptake and metabolism in bacteria. Met. Ions Life Sci. 12:279–332 [Google Scholar]
  2. Archer SL. 2.  2013. Mitochondrial dynamics—mitochondrial fission and fusion in human diseases. N. Engl. J. Med. 369:2236–51 [Google Scholar]
  3. Wang Z, Wu M. 3.  2015. An integrated phylogenomic approach toward pinpointing the origin of mitochondria. Sci. Rep. 5:7949 [Google Scholar]
  4. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T. 4.  et al. 2010. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–7 [Google Scholar]
  5. Danial NN, Korsmeyer SJ. 5.  2004. Cell death: critical control points. Cell 116:205–19 [Google Scholar]
  6. Frey TG, Renken CW, Perkins GA. 6.  2002. Insight into mitochondrial structure and function from electron tomography. Biochim. Biophys. Acta 1555:196–203 [Google Scholar]
  7. Vance JE. 7.  1990. Phospholipid synthesis in a membrane fraction associated with mitochondria. J. Biol. Chem. 265:7248–56 [Google Scholar]
  8. Wenz LS, Opalinski L, Wiedemann N, Becker T. 8.  2015. Cooperation of protein machineries in mitochondrial protein sorting. Biochim. Biophys. Acta 1853:1119–29 [Google Scholar]
  9. Kuznetsov AV, Margreiter R. 9.  2009. Heterogeneity of mitochondria and mitochondrial function within cells as another level of mitochondrial complexity. Int. J. Mol. Sci. 10:1911–29 [Google Scholar]
  10. Errington J. 10.  2015. Bacterial morphogenesis and the enigmatic MreB helix. Nat. Rev. Microbiol. 13:241–48 [Google Scholar]
  11. Polianskyte Z, Peitsaro N, Dapkunas A, Liobikas J, Soliymani R. 11.  et al. 2009. LACTB is a filament-forming protein localized in mitochondria. PNAS 106:18960–65 [Google Scholar]
  12. Vogel F, Bornhovd C, Neupert W, Reichert AS. 12.  2006. Dynamic subcompartmentalization of the mitochondrial inner membrane. J. Cell Biol. 175:237–47 [Google Scholar]
  13. Adams V, Bosch W, Schlegel J, Wallimann T, Brdiczka D. 13.  1989. Further characterization of contact sites from mitochondria of different tissues: topology of peripheral kinases. Biochim. Biophys. Acta 981:213–25 [Google Scholar]
  14. Reichert AS, Neupert W. 14.  2002. Contact sites between the outer and inner membrane of mitochondria—role in protein transport. Biochim. Biophys. Acta 1592:41–49 [Google Scholar]
  15. Brdiczka DG, Zorov DB, Sheu SS. 15.  2006. Mitochondrial contact sites: their role in energy metabolism and apoptosis. Biochim. Biophys. Acta 1762:148–63 [Google Scholar]
  16. Tatsuta T, Scharwey M, Langer T. 16.  2014. Mitochondrial lipid trafficking. Trends Cell Biol. 24:44–52 [Google Scholar]
  17. Perkins G, Renken C, Martone ME, Young SJ, Ellisman M, Frey T. 17.  1997. Electron tomography of neuronal mitochondria: three-dimensional structure and organization of cristae and membrane contacts. J. Struct. Biol. 119:260–72 [Google Scholar]
  18. Mannella CA. 18.  2006. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim. Biophys. Acta 1763:542–48 [Google Scholar]
  19. Hoppins S, Collins SR, Cassidy-Stone A, Hummel E, Devay RM. 19.  et al. 2011. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria. J. Cell Biol. 195:323–40 [Google Scholar]
  20. Harner M, Korner C, Walther D, Mokranjac D, Kaesmacher J. 20.  et al. 2011. The mitochondrial contact site complex, a determinant of mitochondrial architecture. EMBO J. 30:4356–70 [Google Scholar]
  21. von der Malsburg K, Muller JM, Bohnert M, Oeljeklaus S, Kwiatkowska P. 21.  et al. 2011. Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis. Dev. Cell 21:694–707 [Google Scholar]
  22. Bohnert M, Zerbes RM, Davies KM, Muhleip AW, Rampelt H. 22.  et al. 2015. Central role of Mic10 in the mitochondrial contact site and cristae organizing system. Cell Metab. 21:747–55 [Google Scholar]
  23. Barbot M, Jans DC, Schulz C, Denkert N, Kroppen B. 23.  et al. 2015. Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions. Cell Metab. 21:756–63 [Google Scholar]
  24. Friedman JR, Mourier A, Yamada J, McCaffery JM, Nunnari J. 24.  2015. MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture. ELife doi: 10.7554/eLife.07739
  25. Komeili A, Li Z, Newman DK, Jensen GJ. 25.  2006. Magnetosomes are cell membrane invaginations organized by the actin-like protein MamK. Science 311:242–45 [Google Scholar]
  26. Zick M, Rabl R, Reichert AS. 26.  2009. Cristae formation—linking ultrastructure and function of mitochondria. Biochim. Biophys. Acta 1793:5–19 [Google Scholar]
  27. Kopek BG, Shtengel G, Grimm JB, Clayton DA, Hess HF. 27.  2013. Correlative photoactivated localization and scanning electron microscopy. PLOS ONE 8:e77209 [Google Scholar]
  28. Cogliati S, Frezza C, Soriano ME, Varanita T, Quintana-Cabrera R. 28.  et al. 2013. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155:160–71 [Google Scholar]
  29. Gilkerson RW, Selker JM, Capaldi RA. 29.  2003. The cristal membrane of mitochondria is the principal site of oxidative phosphorylation. FEBS Lett. 546:355–58 [Google Scholar]
  30. Arechaga I. 30.  2013. Membrane invaginations in bacteria and mitochondria: common features and evolutionary scenarios. J. Mol. Microbiol. Biotechnol. 23:13–23 [Google Scholar]
  31. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB. 31.  et al. 2008. A mitochondrial protein compendium elucidates complex I disease biology. Cell 134:112–23 [Google Scholar]
  32. Hackenbrock CR. 32.  1968. Ultrastructural bases for metabolically linked mechanical activity in mitochondria. II. Electron transport–linked ultrastructural transformations in mitochondria. J. Cell Biol. 37:345–69 [Google Scholar]
  33. Hackenbrock CR. 33.  1966. Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria. J. Cell Biol. 30:269–97 [Google Scholar]
  34. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA. 34.  2004. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res. 64:985–93 [Google Scholar]
  35. Patten DA, Wong J, Khacho M, Soubannier V, Mailloux RJ. 35.  et al. 2014. OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand. EMBO J. 33:2676–91 [Google Scholar]
  36. Gomes LC, Scorrano L. 36.  2011. Mitochondrial elongation during autophagy: a stereotypical response to survive in difficult times. Autophagy 7:1251–53 [Google Scholar]
  37. Gomes LC, Di Benedetto G, Scorrano L. 37.  2011. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat. Cell Biol. 13:589–98 [Google Scholar]
  38. Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV. 38.  et al. 2006. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126:177–89 [Google Scholar]
  39. Cipolat S, Rudka T, Hartmann D, Costa V, Serneels L. 39.  et al. 2006. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126:163–75 [Google Scholar]
  40. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA. 40.  et al. 2002. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev. Cell 2:55–67 [Google Scholar]
  41. Picard M, McManus MJ, Csordas G, Varnai P, Dorn GW 2nd. 41.  et al. 2015. Trans-mitochondrial coordination of cristae at regulated membrane junctions. Nat. Commun. 6:6259 [Google Scholar]
  42. Daum B, Walter A, Horst A, Osiewacz HD, Kuhlbrandt W. 42.  2013. Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria. PNAS 110:15301–6 [Google Scholar]
  43. Faccenda D, Tan CH, Seraphim A, Duchen MR, Campanella M. 43.  2013. IF1 limits the apoptotic-signalling cascade by preventing mitochondrial remodelling. Cell Death Differ. 20:686–97 [Google Scholar]
  44. Wong ED, Wagner JA, Gorsich SW, McCaffery JM, Shaw JM, Nunnari J. 44.  2000. The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J. Cell Biol. 151:341–52 [Google Scholar]
  45. Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L. 45.  2004. OPA1 requires mitofusin 1 to promote mitochondrial fusion. PNAS 101:15927–32 [Google Scholar]
  46. Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C. 46.  et al. 2000. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat. Genet. 26:207–10 [Google Scholar]
  47. Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S. 47.  et al. 2000. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat. Genet. 26:211–15 [Google Scholar]
  48. Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferre M. 48.  et al. 2009. OPA1-associated disorders: phenotypes and pathophysiology. Int. J. Biochem. Cell Biol. 41:1855–65 [Google Scholar]
  49. Carelli V, Musumeci O, Caporali L, Zanna C, La Morgia C. 49.  et al. 2015. Syndromic parkinsonism and dementia associated with OPA1 missense mutations. Ann. Neurol. 78:21–38 [Google Scholar]
  50. Olichon A, Elachouri G, Baricault L, Delettre C, Belenguer P, Lenaers G. 50.  2007. OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis. Cell Death Differ. 14:682–92 [Google Scholar]
  51. Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B. 51.  et al. 2001. Mutation spectrum and splicing variants in the OPA1 gene. Hum. Genet. 109:584–91 [Google Scholar]
  52. Griparic L, Kanazawa T, van der Bliek AM. 52.  2007. Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage. J. Cell Biol. 178:757–64 [Google Scholar]
  53. Song Z, Chen H, Fiket M, Alexander C, Chan DC. 53.  2007. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J. Cell Biol. 178:749–55 [Google Scholar]
  54. Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM. 54.  2009. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J. Cell Biol. 187:959–66 [Google Scholar]
  55. Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S. 55.  et al. 2009. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J. Cell Biol. 187:1023–36 [Google Scholar]
  56. Olichon A, Baricault L, Gas N, Guillou E, Valette A. 56.  et al. 2003. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J. Biol. Chem. 278:7743–46 [Google Scholar]
  57. Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM. 57.  2004. Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J. Biol. Chem. 279:18792–98 [Google Scholar]
  58. Meeusen S, DeVay R, Block J, Cassidy-Stone A, Wayson S. 58.  et al. 2006. Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127:383–95 [Google Scholar]
  59. Varanita T, Soriano ME, Romanello V, Zaglia T, Quintana-Cabrera R. 59.  et al. 2015. The Opa1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage. Cell Metab. 21:834–44 [Google Scholar]
  60. Anand R, Wai T, Baker MJ, Kladt N, Schauss AC. 60.  et al. 2014. The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J. Cell Biol. 204:919–29 [Google Scholar]
  61. Zick M, Duvezin-Caubet S, Schafer A, Vogel F, Neupert W, Reichert AS. 61.  2009. Distinct roles of the two isoforms of the dynamin-like GTPase Mgm1 in mitochondrial fusion. FEBS Lett. 583:2237–43 [Google Scholar]
  62. Yamaguchi R, Lartigue L, Perkins G, Scott RT, Dixit A. 62.  et al. 2008. Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol. Cell 31:557–69 [Google Scholar]
  63. Mishra P, Carelli V, Manfredi G, Chan DC. 63.  2014. Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab. 19:630–41 [Google Scholar]
  64. Santel A, Fuller MT. 64.  2001. Control of mitochondrial morphology by a human mitofusin. J. Cell Sci. 114:867–74 [Google Scholar]
  65. Hermann GJ, Thatcher JW, Mills JP, Hales KG, Fuller MT. 65.  et al. 1998. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J. Cell Biol. 143:359–73 [Google Scholar]
  66. Hales KG, Fuller MT. 66.  1997. Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 90:121–29 [Google Scholar]
  67. Jakobs S, Martini N, Schauss AC, Egner A, Westermann B, Hell SW. 67.  2003. Spatial and temporal dynamics of budding yeast mitochondria lacking the division component Fis1p. J. Cell Sci. 116:2005–14 [Google Scholar]
  68. Nunnari J, Marshall WF, Straight A, Murray A, Sedat JW, Walter P. 68.  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 8:1233–42 [Google Scholar]
  69. Legros F, Lombes A, Frachon P, Rojo M. 69.  2002. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol. Biol. Cell 13:4343–54 [Google Scholar]
  70. Schauss AC, Huang H, Choi SY, Xu L, Soubeyrand S. 70.  et al. 2010. A novel cell-free mitochondrial fusion assay amenable for high-throughput screenings of fusion modulators. BMC Biol. 8:100 [Google Scholar]
  71. Meeusen S, McCaffery JM, Nunnari J. 71.  2004. Mitochondrial fusion intermediates revealed in vitro. Science 305:1747–52 [Google Scholar]
  72. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. 72.  2003. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J. Cell Biol. 160:189–200 [Google Scholar]
  73. Davies VJ, Hollins AJ, Piechota MJ, Yip W, Davies JR. 73.  et al. 2007. Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. Hum. Mol. Genet. 16:1307–18 [Google Scholar]
  74. Mattenberger Y, James DI, Martinou JC. 74.  2003. Fusion of mitochondria in mammalian cells is dependent on the mitochondrial inner membrane potential and independent of microtubules or actin. FEBS Lett. 538:53–59 [Google Scholar]
  75. Song Z, Ghochani M, McCaffery JM, Frey TG, Chan DC. 75.  2009. Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol. Biol. Cell 20:3525–32 [Google Scholar]
  76. Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC. 76.  2004. Structural basis of mitochondrial tethering by mitofusin complexes. Science 305:858–62 [Google Scholar]
  77. Ishihara N, Eura Y, Mihara K. 77.  2004. Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. J. Cell Sci. 117:6535–46 [Google Scholar]
  78. Malka F, Guillery O, Cifuentes-Diaz C, Guillou E, Belenguer P. 78.  et al. 2005. Separate fusion of outer and inner mitochondrial membranes. EMBO Rep. 6:853–59 [Google Scholar]
  79. Cagalinec M, Safiulina D, Liiv M, Liiv J, Choubey V. 79.  et al. 2013. Principles of the mitochondrial fusion and fission cycle in neurons. J. Cell Sci. 126:2187–97 [Google Scholar]
  80. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD. 80.  et al. 2008. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433–46 [Google Scholar]
  81. Chan DC. 81.  2012. Fusion and fission: interlinked processes critical for mitochondrial health. Annu. Rev. Genet. 46:265–87 [Google Scholar]
  82. Narendra DP, Youle RJ. 82.  2011. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid. Redox Signal. 14:1929–38 [Google Scholar]
  83. Youle RJ, Narendra DP. 83.  2011. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 12:9–14 [Google Scholar]
  84. Enriquez JA, Cabezas-Herrera J, Bayona-Bafaluy MP, Attardi G. 84.  2000. Very rare complementation between mitochondria carrying different mitochondrial DNA mutations points to intrinsic genetic autonomy of the organelles in cultured human cells. J. Biol. Chem. 275:11207–15 [Google Scholar]
  85. Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA. 85.  et al. 2010. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell 141:280–89 [Google Scholar]
  86. Chen H, McCaffery JM, Chan DC. 86.  2007. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell 130:548–62 [Google Scholar]
  87. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ. 87.  et al. 2011. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum. Mol. Genet. 20:1726–37 [Google Scholar]
  88. Leboucher GP, Tsai YC, Yang M, Shaw KC, Zhou M. 88.  et al. 2012. Stress-induced phosphorylation and proteasomal degradation of mitofusin 2 facilitates mitochondrial fragmentation and apoptosis. Mol. Cell 47:547–57 [Google Scholar]
  89. Pyakurel A, Savoia C, Hess D, Scorrano L. 89.  2015. Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis. Mol. Cell 58:244–54 [Google Scholar]
  90. Eura Y, Ishihara N, Oka T, Mihara K. 90.  2006. Identification of a novel protein that regulates mitochondrial fusion by modulating mitofusin (Mfn) protein function. J. Cell Sci. 119:4913–25 [Google Scholar]
  91. Shutt T, Geoffrion M, Milne R, McBride HM. 91.  2012. The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep. 13:909–15 [Google Scholar]
  92. Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT. 92.  2003. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J. Cell Sci. 116:2763–74 [Google Scholar]
  93. Rojo MM, Martin J, Grauby S, Borca-Tasciuc T, Dilhaire S, Martin-Gonzalez M. 93.  2014. Decrease in thermal conductivity in polymeric P3HT nanowires by size-reduction induced by crystal orientation: new approaches towards thermal transport engineering of organic materials. Nanoscale 6:7858–65 [Google Scholar]
  94. Rojo M, Legros F, Chateau D, Lombes A. 94.  2002. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J. Cell Sci. 115:1663–74 [Google Scholar]
  95. Jahn R, Scheller RH. 95.  2006. SNAREs—engines for membrane fusion. Nat. Rev. Mol. Cell Biol. 7:631–43 [Google Scholar]
  96. Eura Y, Ishihara N, Yokota S, Mihara K. 96.  2003. Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. J. Biochem. 134:333–44 [Google Scholar]
  97. Detmer SA, Chan DC. 97.  2007. Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J. Cell Biol. 176:405–14 [Google Scholar]
  98. Hoppins S, Edlich F, Cleland MM, Banerjee S, McCaffery JM. 98.  et al. 2011. The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes. Mol. Cell 41:150–60 [Google Scholar]
  99. de Brito OM, Scorrano L. 99.  2008. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456:605–10 [Google Scholar]
  100. Dorn GW 2nd, Maack C. 100.  2013. SR and mitochondria: calcium cross-talk between kissing cousins. J. Mol. Cell. Cardiol. 55:42–49 [Google Scholar]
  101. Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J. 101.  et al. 2004. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat. Genet. 36:449–51 [Google Scholar]
  102. Polke JM, Laura M, Pareyson D, Taroni F, Milani M. 102.  et al. 2011. Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations. Neurology 77:168–73 [Google Scholar]
  103. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T. 103.  et al. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA–induced innate antiviral responses. Nat. Immunol. 5:730–37 [Google Scholar]
  104. Chen H, Chomyn A, Chan DC. 104.  2005. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J. Biol. Chem. 280:26185–92 [Google Scholar]
  105. Tondera D, Grandemange S, Jourdain A, Karbowski M, Mattenberger Y. 105.  et al. 2009. SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J. 28:1589–600 [Google Scholar]
  106. Ban T, Heymann JA, Song Z, Hinshaw JE, Chan DC. 106.  2010. OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation. Hum. Mol. Genet. 19:2113–22 [Google Scholar]
  107. Hoppins S, Horner J, Song C, McCaffery JM, Nunnari J. 107.  2009. Mitochondrial outer and inner membrane fusion requires a modified carrier protein. J. Cell Biol. 184:569–81 [Google Scholar]
  108. Sesaki H, Jensen RE. 108.  2004. Ugo1p links the Fzo1p and Mgm1p GTPases for mitochondrial fusion. J. Biol. Chem. 279:28298–303 [Google Scholar]
  109. Sesaki H, Jensen RE. 109.  2001. UGO1 encodes an outer membrane protein required for mitochondrial fusion. J. Cell Biol. 152:1123–34 [Google Scholar]
  110. van der Bliek AM, Shen Q, Kawajiri S. 110.  2013. Mechanisms of mitochondrial fission and fusion. Cold Spring Harb. Perspect. Biol. 5:a011072 [Google Scholar]
  111. Hoppins S, Lackner L, Nunnari J. 111.  2007. The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76:751–80 [Google Scholar]
  112. Ingerman E, Perkins EM, Marino M, Mears JA, McCaffery JM. 112.  et al. 2005. Dnm1 forms spirals that are structurally tailored to fit mitochondria. J. Cell Biol. 170:1021–27 [Google Scholar]
  113. Mears JA, Lackner LL, Fang S, Ingerman E, Nunnari J, Hinshaw JE. 113.  2011. Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nat. Struct. Mol. Biol. 18:20–26 [Google Scholar]
  114. Schmidt R, Wurm CA, Punge A, Egner A, Jakobs S, Hell SW. 114.  2009. Mitochondrial cristae revealed with focused light. Nano Lett. 9:2508–10 [Google Scholar]
  115. Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK. 115.  2011. ER tubules mark sites of mitochondrial division. Science 334:358–62 [Google Scholar]
  116. Korobova F, Gauvin TJ, Higgs HN. 116.  2014. A role for myosin II in mammalian mitochondrial fission. Curr. Biol. 24:409–14 [Google Scholar]
  117. Korobova F, Ramabhadran V, Higgs HN. 117.  2013. An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2. Science 339:464–67 [Google Scholar]
  118. De Vos KJ, Allan VJ, Grierson AJ, Sheetz MP. 118.  2005. Mitochondrial function and actin regulate dynamin-related protein 1–dependent mitochondrial fission. Curr. Biol. 15:678–83 [Google Scholar]
  119. Arasaki K, Shimizu H, Mogari H, Nishida N, Hirota N. 119.  et al. 2015. A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division. Dev. Cell 32:304–17 [Google Scholar]
  120. Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT. 120.  2013. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J. Biol. Chem. 288:27584–93 [Google Scholar]
  121. Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S. 121.  et al. 2010. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J. Cell Biol. 191:1141–58 [Google Scholar]
  122. Gandre-Babbe S, van der Bliek AM. 122.  2008. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol. Biol. Cell 19:2402–12 [Google Scholar]
  123. James DI, Parone PA, Mattenberger Y, Martinou JC. 123.  2003. hFis1, a novel component of the mammalian mitochondrial fission machinery. J. Biol. Chem. 278:36373–79 [Google Scholar]
  124. Mozdy AD, McCaffery JM, Shaw JM. 124.  2000. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J. Cell Biol. 151:367–80 [Google Scholar]
  125. Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT. 125.  2011. MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep. 12:565–73 [Google Scholar]
  126. Yoon Y, Krueger EW, Oswald BJ, McNiven MA. 126.  2003. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol. Cell. Biol. 23:5409–20 [Google Scholar]
  127. Zhao J, Liu T, Jin S, Wang X, Qu M. 127.  et al. 2011. Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission. EMBO J. 30:2762–78 [Google Scholar]
  128. Koirala S, Guo Q, Kalia R, Bui HT, Eckert DM. 128.  et al. 2013. Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission. PNAS 110:E1342–51 [Google Scholar]
  129. Loson OC, Song Z, Chen H, Chan DC. 129.  2013. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol. Biol. Cell 24:659–67 [Google Scholar]
  130. Shen Q, Yamano K, Head BP, Kawajiri S, Cheung JT. 130.  et al. 2014. Mutations in Fis1 disrupt orderly disposal of defective mitochondria. Mol. Biol. Cell 25:145–59 [Google Scholar]
  131. Gomes LC, Scorrano L. 131.  2008. High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim. Biophys. Acta 1777:860–66 [Google Scholar]
  132. Yamano K, Fogel AI, Wang C, van der Bliek AM, Youle RJ. 132.  2014. Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy. ELife 3:e01612 [Google Scholar]
  133. Richter V, Palmer CS, Osellame LD, Singh AP, Elgass K. 133.  et al. 2014. Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission. J. Cell Biol. 204:477–86 [Google Scholar]
  134. Legesse-Miller A, Massol RH, Kirchhausen T. 134.  2003. Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol. Biol. Cell 14:1953–63 [Google Scholar]
  135. Twig G, Graf SA, Wikstrom JD, Mohamed H, Haigh SE. 135.  et al. 2006. Tagging and tracking individual networks within a complex mitochondrial web with photoactivatable GFP. Am. J. Physiol. Cell Physiol. 291:C176–84 [Google Scholar]
  136. Labrousse AM, Zappaterra MD, Rube DA, van der Bliek AM. 136.  1999. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol. Cell 4:815–26 [Google Scholar]
  137. Jakobs S, Schauss AC, Hell SW. 137.  2003. Photoconversion of matrix targeted GFP enables analysis of continuity and intermixing of the mitochondrial lumen. FEBS Lett. 554:194–200 [Google Scholar]
  138. Otsuga D, Keegan BR, Brisch E, Thatcher JW, Hermann GJ. 138.  et al. 1998. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J. Cell Biol. 143:333–49 [Google Scholar]
  139. Elgass K, Pakay J, Ryan MT, Palmer CS. 139.  2013. Recent advances into the understanding of mitochondrial fission. Biochim. Biophys. Acta 1833:150–61 [Google Scholar]
  140. Stavru F, Palmer AE, Wang C, Youle RJ, Cossart P. 140.  2013. Atypical mitochondrial fission upon bacterial infection. PNAS 110:16003–8 [Google Scholar]
  141. Cereghetti GM, Stangherlin A, Martins de Brito O, Chang CR, Blackstone C. 141.  et al. 2008. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. PNAS 105:15803–8 [Google Scholar]
  142. Cribbs JT, Strack S. 142.  2007. Reversible phosphorylation of Drp1 by cyclic AMP–dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 8:939–44 [Google Scholar]
  143. Chang CR, Blackstone C. 143.  2007. Cyclic AMP–dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J. Biol. Chem. 282:21583–87 [Google Scholar]
  144. Costa V, Giacomello M, Hudec R, Lopreiato R, Ermak G. 144.  et al. 2010. Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli. EMBO Mol. Med. 2:490–503 [Google Scholar]
  145. Chang CR, Manlandro CM, Arnoult D, Stadler J, Posey AE. 145.  et al. 2010. A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division. J. Biol. Chem. 285:32494–503 [Google Scholar]
  146. Bi EF, Lutkenhaus J. 146.  1991. FtsZ ring structure associated with division in Escherichia coli. Nature 354:161–64 [Google Scholar]
  147. Goehring NW, Beckwith J. 147.  2005. Diverse paths to midcell: assembly of the bacterial cell division machinery. Curr. Biol 15:R514–26 [Google Scholar]
  148. Beech PL, Gilson PR. 148.  2000. FtsZ and organelle division in Protists. Protist 151:11–16 [Google Scholar]
  149. Beech PL, Nheu T, Schultz T, Herbert S, Lithgow T. 149.  et al. 2000. Mitochondrial FtsZ in a chromophyte alga. Science 287:1276–79 [Google Scholar]
  150. Purkanti R, Thattai M. 150.  2015. Ancient dynamin segments capture early stages of host-mitochondrial integration. PNAS 112:2800–5 [Google Scholar]
  151. Katajisto P, Dohla J, Chaffer CL, Pentinmikko N, Marjanovic N. 151.  et al. 2015. Stem cells. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science 348:340–43 [Google Scholar]
  152. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES. 152.  et al. 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 16:3–11 [Google Scholar]
  153. White MJ, McArthur K, Metcalf D, Lane RM, Cambier JC. 153.  et al. 2014. Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159:1549–62 [Google Scholar]
  154. Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG. 154.  et al. 2001. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1:515–25 [Google Scholar]
  155. Antignani A, Youle RJ. 155.  2006. How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane?. Curr. Opin. Cell Biol. 18:685–89 [Google Scholar]
  156. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A. 156.  et al. 2000. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 14:2060–71 [Google Scholar]
  157. Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH. 157.  2000. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 7:1166–73 [Google Scholar]
  158. Zou H, Li Y, Liu X, Wang X. 158.  1999. An APAF-1·cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem. 274:11549–56 [Google Scholar]
  159. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M. 159.  et al. 1997. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–89 [Google Scholar]
  160. Estaquier J, Arnoult D. 160.  2007. Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. Cell Death Differ. 14:1086–94 [Google Scholar]
  161. Lee YJ, Jeong SY, Karbowski M, Smith CL, Youle RJ. 161.  2004. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol. Biol. Cell 15:5001–11 [Google Scholar]
  162. Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C. 162.  et al. 2008. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev. Cell 14:193–204 [Google Scholar]
  163. Li J, Zhou J, Li Y, Qin D, Li P. 163.  2010. Mitochondrial fission controls DNA fragmentation by regulating endonuclease G. Free Radic. Biol. Med. 49:622–31 [Google Scholar]
  164. Arnoult D. 164.  2007. Mitochondrial fragmentation in apoptosis. Trends Cell Biol. 17:6–12 [Google Scholar]
  165. Montessuit S, Somasekharan SP, Terrones O, Lucken-Ardjomande S, Herzig S. 165.  et al. 2010. Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization. Cell 142:889–901 [Google Scholar]
  166. Renault TT, Floros KV, Elkholi R, Corrigan KA, Kushnareva Y. 166.  et al. 2015. Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis. Mol. Cell 57:69–82 [Google Scholar]
  167. Kim SJ, Syed GH, Khan M, Chiu WW, Sohail MA. 167.  et al. 2014. Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. PNAS 111:6413–18 [Google Scholar]
  168. Weaver D, Eisner V, Liu X, Varnai P, Hunyady L. 168.  et al. 2014. Distribution and apoptotic function of outer membrane proteins depend on mitochondrial fusion. Mol. Cell 54:870–78 [Google Scholar]
  169. Bernardi P, Azzone GF. 169.  1981. Cytochrome c as an electron shuttle between the outer and inner mitochondrial membranes. J. Biol. Chem. 256:7187–92 [Google Scholar]
  170. Merkwirth C, Dargazanli S, Tatsuta T, Geimer S, Lower B. 170.  et al. 2008. Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes Dev. 22:476–88 [Google Scholar]
  171. Onoguchi K, Onomoto K, Takamatsu S, Jogi M, Takemura A. 171.  et al. 2010. Virus-infection or 5′ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1. PLOS Pathog. 6:e1001012 [Google Scholar]
  172. Castanier C, Garcin D, Vazquez A, Arnoult D. 172.  2010. Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway. EMBO Rep. 11:133–38 [Google Scholar]
  173. Johnson LV, Walsh ML, Chen LB. 173.  1980. Localization of mitochondria in living cells with rhodamine 123. PNAS 77:990–94 [Google Scholar]
  174. Seth RB, Sun L, Ea CK, Chen ZJ. 174.  2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF 3. Cell 122:669–82 [Google Scholar]
  175. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. 175.  2005. VISA is an adapter protein required for virus-triggered IFN-β signaling. Mol. Cell 19:727–40 [Google Scholar]
  176. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M. 176.  et al. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167–72 [Google Scholar]
  177. Kawai T, Takahashi K, Sato S, Coban C, Kumar H. 177.  et al. 2005. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 6:981–88 [Google Scholar]
  178. West AP, Shadel GS, Ghosh S. 178.  2011. Mitochondria in innate immune responses. Nat. Rev. Immunol. 11:389–402 [Google Scholar]
  179. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C. 179.  et al. 2010. Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141:668–81 [Google Scholar]
  180. Koshiba T, Yasukawa K, Yanagi Y, Kawabata S. 180.  2011. Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling. Sci. Signal. 4:ra7 [Google Scholar]
  181. Zemirli N, Pourcelot M, Ambroise G, Hatchi E, Vazquez A, Arnoult D. 181.  2014. Mitochondrial hyperfusion promotes NF-κB activation via the mitochondrial E3 ligase MULAN. FEBS J. 281:3095–112 [Google Scholar]
  182. Lum M, Morona R. 182.  2014. Dynamin-related protein Drp1 and mitochondria are important for Shigella flexneri infection. Int. J. Med. Microbiol. 304:530–41 [Google Scholar]
  183. Yasukawa K, Oshiumi H, Takeda M, Ishihara N, Yanagi Y. 183.  et al. 2009. Mitofusin 2 inhibits mitochondrial antiviral signaling. Sci. Signal. 2:ra47 [Google Scholar]
  184. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. 184.  2011. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 146:448–61 [Google Scholar]
  185. Ishikawa H, Barber GN. 185.  2008. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:674–78 [Google Scholar]
  186. Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J. 186.  et al. 2007. T cell activation requires mitochondrial translocation to the immunological synapse. PNAS 104:14418–23 [Google Scholar]
  187. Baixauli F, Martin-Cofreces NB, Morlino G, Carrasco YR, Calabia-Linares C. 187.  et al. 2011. The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse. EMBO J. 30:1238–50 [Google Scholar]
  188. Pernas L, Adomako-Ankomah Y, Shastri AJ, Ewald SE, Treeck M. 188.  et al. 2014. Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLOS Biol. 12:e1001845 [Google Scholar]
  189. Ferreira-da-Silva A, Valacca C, Rios E, Pópulo H, Soares P. 189.  et al. 2015. Mitochondrial dynamics protein Drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration. PLOS ONE 10:e0122308 [Google Scholar]
  190. Campello S, Lacalle RA, Bettella M, Manes S, Scorrano L, Viola A. 190.  2006. Orchestration of lymphocyte chemotaxis by mitochondrial dynamics. J. Exp. Med. 203:2879–86 [Google Scholar]
  191. Zhao J, Zhang J, Yu M, Xie Y, Huang Y. 191.  et al. 2013. Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene 32:4814–24 [Google Scholar]
  192. Desai SP, Bhatia SN, Toner M, Irimia D. 192.  2013. Mitochondrial localization and the persistent migration of epithelial cancer cells. Biophys. J. 104:2077–88 [Google Scholar]
  193. Reggiori F, Klionsky DJ. 193.  2002. Autophagy in the eukaryotic cell. Eukaryot. Cell 1:11–21 [Google Scholar]
  194. Mizushima N. 194.  2007. Autophagy: process and function. Genes Dev. 21:2861–73 [Google Scholar]
  195. Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J. 195.  2011. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. PNAS 108:10190–95 [Google Scholar]
  196. Rambold AS, Cohen S, Lippincott-Schwartz J. 196.  2015. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev. Cell 32:678–92 [Google Scholar]
  197. Wakabayashi J, Zhang Z, Wakabayashi N, Tamura Y, Fukaya M. 197.  et al. 2009. The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186:805–16 [Google Scholar]
  198. Malassine A, Frendo JL, Evain-Brion D. 198.  2003. A comparison of placental development and endocrine functions between the human and mouse model. Hum. Reprod. Update 9:531–39 [Google Scholar]
  199. Martinez F, Kiriakidou M, Strauss JF 3rd. 199.  1997. Structural and functional changes in mitochondria associated with trophoblast differentiation: methods to isolate enriched preparations of syncytiotrophoblast mitochondria. Endocrinology 138:2172–83 [Google Scholar]
  200. Wasilewski M, Semenzato M, Rafelski SM, Robbins J, Bakardjiev AI, Scorrano L. 200.  2012. Optic atrophy 1–dependent mitochondrial remodeling controls steroidogenesis in trophoblasts. Curr. Biol. 22:1228–34 [Google Scholar]
  201. Udagawa O, Ishihara T, Maeda M, Matsunaga Y, Tsukamoto S. 201.  et al. 2014. Mitochondrial fission factor Drp1 maintains oocyte quality via dynamic rearrangement of multiple organelles. Curr. Biol. 24:2451–58 [Google Scholar]
  202. Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I. 202.  et al. 2015. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J. Cell Biol. 208:429–42 [Google Scholar]
  203. Kasahara A, Cipolat S, Chen Y, Dorn GW. Scorrano L. 203.  2nd, 2013. Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling. Science 342:734–37 [Google Scholar]
  204. Son MJ, Kwon Y, Son MY, Seol B, Choi HS. 204.  et al. 2015. Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency. Cell Death Differ. 221957–69
  205. Son MY, Choi H, Han YM, Cho YS. 205.  2013. Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency. Stem Cells 31:2374–87 [Google Scholar]
  206. Civiletto G, Varanita T, Cerutti R, Gorletta T, Barbaro S. 206.  et al. 2015. Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models. Cell Metab. 21:845–54 [Google Scholar]
  207. Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO. 207.  et al. 2009. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat. Cell Biol. 11:958–66 [Google Scholar]
  208. Oettinghaus B, Schulz JM, Restelli LM, Licci M, Savoia C. 208.  et al. 2015. Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. Cell Death Differ. In press
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