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Mitochondrial Dynamics: A Journey from Mitochondrial Morphology to Mitochondrial Function and Quality

  • David Sebastián
  • Antonio Zorzano
Chapter

Abstract

Mitochondria were considered in the past as static and isolated organelles inside the cell. However, currently it is clear that they change in shape, and they are continuously moving along the cell forming an interconnected and highly dynamic network. The sum of all these processes are referred to as mitochondrial dynamics. In addition to the control of mitochondrial morphology and movement, a large number of evidences have turned mitochondrial dynamics into a key factor controlling mitochondrial function and quality, having an important role in respiration, oxidative metabolism, Ca2+ homeostasis, mitochondrial quality control, autophagy and apoptosis. The importance of mitochondrial dynamics in physiology is reflected by the increasing number of pathologies associated with its dysregulation, such as neuropathies, neurodegenerative diseases, atherosclerosis, metabolic diseases, sarcopenia and aging. Therefore, the factors regulating mitochondrial dynamics and the understanding of the molecular mechanisms by which mitochondrial dynamics regulates key aspects of mitochondrial biology is of great importance. In this chapter, we will focus on the proteins involved in mitochondrial dynamics, their regulation and their impact in the control of mitochondrial function and quality.

Keywords

Mitochondria Dynamics Morphology Neurodegenerative diseases Mitochondrial quality control 

References

  1. Anand R, Wai T, Baker MJ, Kladt N, Schauss AC, Rugarli E, Langer T (2014) The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol 204:919–929CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J, Daugaard JR, Lloberas J, Camps M, Zierath JR, Rabasa-Lhoret R, Wallberg-Henriksson H, Laville M, Palacin M, Vidal H, Rivera F, Brand M, Zorzano A (2003) Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem 278:17190–17197CrossRefPubMedGoogle Scholar
  3. Braschi E, Zunino R, McBride HM (2009) MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep 10:748–754CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bucha S, Mukhopadhyay D, Bhattacharyya NP (2015) Regulation of mitochondrial morphology and cell cycle by microRNA-214 targeting Mitofusin2. Biochem Biophys Res Commun 465:797–802CrossRefPubMedGoogle Scholar
  5. Buck MD, O’Sullivan D, Klein Geltink RI, Curtis JD, Chang CH, Sanin DE, Qiu J, Kretz O, Braas D, van der Windt GJ, Chen Q, Huang SC, O’Neill CM, Edelson BT, Pearce EJ, Sesaki H, Huber TB, Rambold AS, Pearce EL (2016) Mitochondrial dynamics controls T cell fate through metabolic programming. Cell 166:63–76CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cereghetti GM, Stangherlin A, Martins De Brito O, Chang CR, Blackstone C, Bernardi P, Scorrano L (2008) Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A 105:15803–15808CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chen Y, Dorn GW 2nd (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340:471–475CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280:26185–26192CrossRefPubMedGoogle Scholar
  9. 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 324:102–105CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cogliati S, Frezza C, Soriano ME, Varanita T, Quintana-Cabrera R, Corrado M, Cipolat S, Costa V, Casarin A, Gomes LC, Perales-Clemente E, Salviati L, Fernandez-Silva P, Enriquez JA, Scorrano L (2013) Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155:160–171CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cribbs JT, Strack S (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8:939–944CrossRefPubMedPubMedCentralGoogle Scholar
  12. De Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456:605–610CrossRefPubMedGoogle Scholar
  13. Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B, Faivre L, Lenaers G, Belenguer P, Hamel CP (2001) Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet 109:584–591CrossRefPubMedGoogle Scholar
  14. Din S, Mason M, Volkers M, Johnson B, Cottage CT, Wang Z, Joyo AY, Quijada P, Erhardt P, Magnuson NS, Konstandin MH, Sussman MA (2013) Pim-1 preserves mitochondrial morphology by inhibiting dynamin-related protein 1 translocation. Proc Natl Acad Sci U S A 110:5969–5974CrossRefPubMedPubMedCentralGoogle Scholar
  15. Duvezin-Caubet S, Jagasia R, Wagener J, Hofmann S, Trifunovic A, Hansson A, Chomyn A, Bauer MF, Attardi G, Larsson NG, Neupert W, Reichert AS (2006) Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology. J Biol Chem 281:37972–37979CrossRefPubMedGoogle Scholar
  16. Franco A, Kitsis RN, Fleischer JA, Gavathiotis E, Kornfeld OS, Gong G, Biris N, Benz A, Qvit N, Donnelly SK, Chen Y, Mennerick S, Hodgson L, Mochly-Rosen D, Dorn GW II (2016) Correcting mitochondrial fusion by manipulating mitofusin conformations. Nature 540:74–79CrossRefPubMedPubMedCentralGoogle Scholar
  17. Friedman JR, Lackner LL, West M, Dibenedetto JR, Nunnari J, Voeltz GK (2011) ER tubules mark sites of mitochondrial division. Science 334:358–362CrossRefPubMedPubMedCentralGoogle Scholar
  18. Gawlowski, T., Suarez, J., Scott, B., Torres-Gonzalez, M., Wang, H., Schwappacher, R., Han, X., Yates, J. R. 3rd, , Hoshijima, M. & Dillmann, W. 2012. Modulation of dynamin-related protein 1 (DRP1) function by increased O-linked-beta-N-acetylglucosamine modification (O-GlcNAc) in cardiac myocytes. J Biol Chem, 287, 30024-30034.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 19:4861–4870CrossRefPubMedPubMedCentralGoogle Scholar
  20. Gomes LC, Di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13:589–598CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, Lippincott-Schwartz J (2010) Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141:656–667CrossRefPubMedPubMedCentralGoogle Scholar
  22. Han XJ, Lu YF, Li SA, Kaitsuka T, Sato Y, Tomizawa K, Nairn AC, Takei K, Matsui H, Matsushita M (2008) CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology. J Cell Biol 182:573–585CrossRefPubMedPubMedCentralGoogle Scholar
  23. Ikeda Y, Shirakabe A, Maejima Y, Zhai P, Sciarretta S, Toli J, Nomura M, Mihara K, Egashira K, Ohishi M, Abdellatif M, Sadoshima J (2015) Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress. Circ Res 116:264–278CrossRefPubMedGoogle Scholar
  24. Ishihara N, Fujita Y, Oka T, Mihara K (2006) Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J 25:2966–2977CrossRefPubMedPubMedCentralGoogle Scholar
  25. Karbowski M, Neutzner A, Youle RJ (2007) The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J Cell Biol 178:71–84CrossRefPubMedPubMedCentralGoogle Scholar
  26. Kim H, Scimia MC, Wilkinson D, Trelles RD, Wood MR, Bowtell D, Dillin A, Mercola M, Ronai ZA (2011) Fine-tuning of Drp1/Fis1 availability by AKAP121/Siah2 regulates mitochondrial adaptation to hypoxia. Mol Cell 44:532–544CrossRefPubMedPubMedCentralGoogle Scholar
  27. Koshiba T, Detmer SA, Kaiser JT, Chen H, Mccaffery JM, Chan DC (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305:858–862CrossRefPubMedGoogle Scholar
  28. Kulkarni SS, Joffraud M, Boutant M, Ratajczak J, Gao AW, Maclachlan C, Hernandez-Alvarez MI, Raymond F, Metairon S, Descombes P, Houtkooper RH, Zorzano A, Canto C (2016) Mfn1 deficiency in the liver protects against diet-induced insulin resistance and enhances the hypoglycemic effect of metformin. Diabetes 65:3552–3560CrossRefPubMedGoogle Scholar
  29. Leboucher GP, Tsai YC, Yang M, Shaw KC, Zhou M, Veenstra TD, Glickman MH, Weissman AM (2012) Stress-induced phosphorylation and proteasomal degradation of mitofusin 2 facilitates mitochondrial fragmentation and apoptosis. Mol Cell 47:547–557CrossRefPubMedPubMedCentralGoogle Scholar
  30. Li J, Donath S, Li Y, Qin D, Prabhakar BS, Li P (2010) miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet 6:e1000795CrossRefPubMedPubMedCentralGoogle Scholar
  31. Li J, Li Y, Jiao J, Wang J, Qin D, Li P (2014a) Mitofusin 1 is negatively regulated by microRNA 140 in cardiomyocyte apoptosis. Mol Cell Biol 34:1788–1799CrossRefPubMedPubMedCentralGoogle Scholar
  32. Li X, Wang FS, Wu ZY, Lin JL, Lan WB, Lin JH (2014b) MicroRNA-19b targets Mfn1 to inhibit Mfn1-induced apoptosis in osteosarcoma cells. Neoplasma 61:265–273CrossRefPubMedGoogle Scholar
  33. 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:e3613CrossRefPubMedPubMedCentralGoogle Scholar
  34. Liesa M, Palacin M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89:799–845CrossRefPubMedGoogle Scholar
  35. Lin JR, Shen WL, Yan C, Gao PJ (2015) Downregulation of dynamin-related protein 1 contributes to impaired autophagic flux and angiogenic function in senescent endothelial cells. Arterioscler Thromb Vasc Biol 35:1413–1422CrossRefPubMedGoogle Scholar
  36. Loson OC, Song Z, Chen H, Chan DC (2013) Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 24:659–667CrossRefPubMedPubMedCentralGoogle Scholar
  37. Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Lammermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS, Bouman L, Vogt-Weisenhorn D, Wurst W, Tatzelt J, Haass C, Winklhofer KF (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284:22938–22951CrossRefPubMedPubMedCentralGoogle Scholar
  38. Martorell-Riera A, Segarra-Mondejar M, Munoz JP, Ginet V, Olloquequi J, Perez-Clausell J, Palacin M, Reina M, Puyal J, Zorzano A, Soriano FX (2014) Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. EMBO J 33:2388–2407CrossRefPubMedPubMedCentralGoogle Scholar
  39. Merkwirth C, Dargazanli S, Tatsuta T, Geimer S, Lower B, Wunderlich FT, Von Kleist-Retzow JC, Waisman A, Westermann B, Langer T (2008) Prohibitins control cell proliferation and apoptosis by regulating Opa1-dependent cristae morphogenesis in mitochondria. Genes Dev 22:476–488CrossRefPubMedPubMedCentralGoogle Scholar
  40. Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG (2015) Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J Cell Biol 208:429–442CrossRefPubMedPubMedCentralGoogle Scholar
  41. Nakamura N, Kimura Y, Tokuda M, Honda S, Hirose S (2006) MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep 7:1019–1022CrossRefPubMedPubMedCentralGoogle Scholar
  42. Olichon A, Emorine LJ, Descoins E, Pelloquin L, Brichese L, Gas N, Guillou E, Delettre C, Valette A, Hamel CP, Ducommun B, Lenaers G, Belenguer P (2002) The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett 523:171–176CrossRefPubMedGoogle Scholar
  43. Parra V, Verdejo HE, Iglewski M, Del Campo A, Troncoso R, Jones D, Zhu Y, Kuzmicic J, Pennanen C, Lopez-Crisosto C, Jana F, Ferreira J, Noguera E, Chiong M, Bernlohr DA, Klip A, Hill JA, Rothermel BA, Abel ED, Zorzano A, Lavandero S (2014) Insulin stimulates mitochondrial fusion and function in cardiomyocytes via the Akt-mTOR-NFkappaB-Opa-1 signaling pathway. Diabetes 63:75–88CrossRefPubMedGoogle Scholar
  44. Peng J, Ren KD, Yang J, Luo XJ (2016) Mitochondrial E3 ubiquitin ligase 1: a key enzyme in regulation of mitochondrial dynamics and functions. Mitochondrion 28:49–53CrossRefPubMedGoogle Scholar
  45. Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, Palacin M, Zorzano A (2005) The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet 14:1405–1415CrossRefPubMedGoogle Scholar
  46. 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:e10054CrossRefPubMedPubMedCentralGoogle Scholar
  47. Pyakurel A, Savoia C, Hess D, Scorrano L (2015) Extracellular regulated kinase phosphorylates mitofusin 1 to control mitochondrial morphology and apoptosis. Mol Cell 58:244–254CrossRefPubMedPubMedCentralGoogle Scholar
  48. Qi X, Disatnik MH, Shen N, Sobel RA, Mochly-Rosen D (2011) Aberrant mitochondrial fission in neurons induced by protein kinase C{delta} under oxidative stress conditions in vivo. Mol Biol Cell 22:256–265CrossRefPubMedPubMedCentralGoogle Scholar
  49. Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J (2011) Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci U S A 108:10190–10195CrossRefPubMedPubMedCentralGoogle Scholar
  50. 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 115:1663–1674PubMedGoogle Scholar
  51. Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT (2003) Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci 116:2763–2774CrossRefPubMedGoogle Scholar
  52. Sebastian D, Hernandez-Alvarez MI, Segales J, Sorianello E, Munoz JP, Sala D, Waget A, Liesa M, Paz JC, Gopalacharyulu P, Oresic M, Pich S, Burcelin R, Palacin M, Zorzano A (2012) Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci U S A 109:5523–5528CrossRefPubMedPubMedCentralGoogle Scholar
  53. Sebastian D, Sorianello E, Segales J, Irazoki A, Ruiz-Bonilla V, Sala D, Planet E, Berenguer-Llergo A, Munoz JP, Sanchez-Feutrie M, Plana N, Hernandez-Alvarez MI, Serrano AL, Palacin M, Zorzano A (2016) Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J 35:1677–1693CrossRefPubMedPubMedCentralGoogle Scholar
  54. Sebastian D, Palacin M, Zorzano A (2017) Mitochondrial dynamics: coupling mitochondrial fitness with healthy aging. Trends Mol Med 23:201–215CrossRefPubMedGoogle Scholar
  55. Segales J, Paz JC, Hernandez-Alvarez MI, Sala D, Munoz JP, Noguera E, Pich S, Palacin M, Enriquez JA, Zorzano A (2013) A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells. Am J Physiol Endocrinol Metab 305:E1208–E1221CrossRefPubMedGoogle Scholar
  56. Smirnova E, Griparic L, Shurland DL, Van Der Bliek AM (2001) Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 12:2245–2256CrossRefPubMedPubMedCentralGoogle Scholar
  57. Soriano FX, Liesa M, Bach D, Chan DC, Palacin M, Zorzano A (2006) Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes 55:1783–1791CrossRefPubMedGoogle Scholar
  58. Taguchi N, Ishihara N, Jofuku A, Oka T, Mihara K (2007) Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem 282:11521–11529CrossRefPubMedGoogle Scholar
  59. 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 27:433–446CrossRefPubMedPubMedCentralGoogle Scholar
  60. Wang JX, Jiao JQ, Li Q, Long B, Wang K, Liu JP, Li YR, Li PF (2011) miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat Med 17:71–78CrossRefPubMedGoogle Scholar
  61. Wang W, Wang Y, Long J, Wang J, Haudek SB, Overbeek P, Chang BH, Schumacker PT, Danesh FR (2012) Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells. Cell Metab 15:186–200CrossRefPubMedPubMedCentralGoogle Scholar
  62. Wu H, Li Z, Wang Y, Yang P, Li H, Wu C (2016a) MiR-106b-mediated Mfn2 suppression is critical for PKM2 induced mitochondrial fusion. Am J Cancer Res 6:2221–2234PubMedPubMedCentralGoogle Scholar
  63. Wu W, Lin C, Wu K, Jiang L, Wang X, Li W, Zhuang H, Zhang X, Chen H, Li S, Yang Y, Lu Y, Wang J, Zhu R, Zhang L, Sui S, Tan N, Zhao B, Zhang J, Li L, Feng D (2016b) FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions. EMBO J 35:1368–1384CrossRefPubMedPubMedCentralGoogle Scholar
  64. Yonashiro R, Ishido S, Kyo S, Fukuda T, Goto E, Matsuki Y, Ohmura-Hoshino M, Sada K, Hotta H, Yamamura H, Inatome R, Yanagi S (2006) A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics. EMBO J 25:3618–3626CrossRefPubMedPubMedCentralGoogle Scholar
  65. Yu T, Jhun BS, Yoon Y (2011) High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxid Redox Signal 14:425–437CrossRefPubMedPubMedCentralGoogle Scholar
  66. Zepeda R, Kuzmicic J, Parra V, Troncoso R, Pennanen C, Riquelme JA, Pedrozo Z, Chiong M, Sanchez G, Lavandero S (2014) Drp1 loss-of-function reduces cardiomyocyte oxygen dependence protecting the heart from ischemia-reperfusion injury. J Cardiovasc Pharmacol 63:477–487CrossRefPubMedGoogle Scholar
  67. Zhang Z, Wakabayashi N, Wakabayashi J, Tamura Y, Song WJ, Sereda S, Clerc P, Polster BM, Aja SM, Pletnikov MV, Kensler TW, Shirihai OS, Iijima M, Hussain MA, Sesaki H (2011) The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells. Mol Biol Cell 22:2235–2245CrossRefPubMedPubMedCentralGoogle Scholar
  68. Zhang H, Wang P, Bisetto S, Yoon Y, Chen Q, Sheu SS, Wang W (2017) A novel fission-independent role of dynamin-related protein 1 in cardiac mitochondrial respiration. Cardiovasc Res 113:160–170CrossRefPubMedGoogle Scholar
  69. Zhao T, Huang X, Han L, Wang X, Cheng H, Zhao Y, Chen Q, Chen J, Xiao R, Zheng M (2012) Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J Biol Chem 287:23615–23625CrossRefPubMedPubMedCentralGoogle Scholar
  70. Zhou X, Zhang L, Zheng B, Yan Y, Zhang Y, Xie H, Zhou L, Zheng S, Wang W (2016) MicroRNA-761 is upregulated in hepatocellular carcinoma and regulates tumorigenesis by targeting Mitofusin-2. Cancer Sci 107:424–432CrossRefPubMedPubMedCentralGoogle Scholar
  71. Zunino R, Schauss A, Rippstein P, Andrade-Navarro M, McBride HM (2007) The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. J Cell Sci 120:1178–1188CrossRefPubMedGoogle Scholar
  72. Zuo W, Zhang S, Xia CY, Guo XF, He WB, Chen NH (2014) Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner: the role of inhibition of Drp1 in ischemic brain damage. Neuropharmacology 86:103–115CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Research in Biomedicine (IRB Barcelona)The Barcelona Institute of Science and TechnologyBarcelonaSpain
  2. 2.Departament de Bioquímica i Biomedicina Molecular, Facultat de BiologiaUniversitat de BarcelonaBarcelonaSpain
  3. 3.Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)Instituto de Salud Carlos IIIMadridSpain

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