Skip to main content
SpringerLink
Log in

Mitochondrial Fission in Human Diseases

  • Chapter
  • First Online:
Book cover Pharmacology of Mitochondria

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 240))

Abstract

Mitochondria are an essential component of multicellular life – from primitive organisms, to highly complex entities like mammals. The importance of mitochondria is underlined by their plethora of well-characterized essential functions such as energy production through oxidative phosphorylation (OX-PHOS), calcium and reactive oxygen species (ROS) signaling, and regulation of apoptosis. In addition, novel roles and attributes of mitochondria are coming into focus through the recent years of mitochondrial research. In particular, over the past decade the study of mitochondrial shape and dynamics has achieved special significance, as they are found to impact mitochondrial function. Recent advances indicate that mitochondrial function and dynamics are inter-connected, and maintain the balance between health and disease at a cellular and an organismal level. For example, excessive mitochondrial division (fission) is associated with functional defects, and is implicated in multiple human diseases from neurodegenerative diseases to cancer. In this chapter we examine the recent literature on the mitochondrial dynamics–function relationship, and explore how it impacts on the development and progression of human diseases. We will also highlight the implications of therapeutic manipulation of mitochondrial dynamics in treating various human pathologies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 204:919–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baloh RH, Schmidt RE, Pestronk A, Milbrandt J (2007) Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci 27:422–430

    Article  CAS  PubMed  Google Scholar 

  • Baloyannis SJ (2006) Mitochondrial alterations in Alzheimer’s disease. J Alzheimers Dis 9:119–126

    Article  PubMed  Google Scholar 

  • Barsoum MJ, Yuan H, Gerencser AA, Liot G, Kushnareva Y, Graber S, Kovacs I, Lee WD, Waggoner J, Cui J, White AD, Bossy B, Martinou JC, Youle RJ, Lipton SA, Ellisman MH, Perkins GA, Bossy-Wetzel E (2006) Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J 25:3900–3911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Braschi E, Zunino R, McBride HM (2009) MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep 10:748–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brouillet E, Hantraye P, Ferrante RJ, Dolan R, Leroy-Willig A, Kowall NW, Beal MF (1995) Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci U S A 92:7105–7109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Chang CR, Blackstone C (2007) Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J Biol Chem 282:21583–21587

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Chan DC (2004) Mitochondrial dynamics in mammals. Curr Top Dev Biol 59:119–144

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Liu Y, Dorn GW 2nd (2011) Mitochondrial fusion is essential for organelle function and cardiac homeostasis. Circ Res 109:1327–1331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Ren S, Clish C, Jain M, Mootha V, McCaffery JM, Chan DC (2015) Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy. J Cell Biol 211:795–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR (2010) The BCL-2 family reunion. Mol Cell 37:299–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Chou CH, Lin CC, Yang MC, Wei CC, Liao HD, Lin RC, Tu WY, Kao TC, Hsu CM, Cheng JT, Chou AK, Lee CI, Loh JK, Howng SL, Hong YR (2012) GSK3beta-mediated Drp1 phosphorylation induced elongated mitochondrial morphology against oxidative stress. PLoS One 7, e49112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choudhary V, Kaddour-Djebbar I, Lakshmikanthan V, Ghazaly T, Thangjam GS, Sreekumar A, Lewis RW, Mills IG, Bollag WB, Kumar MV (2011) Novel role of androgens in mitochondrial fission and apoptosis. Mol Cancer Res 9:1067–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cipolat S, Rudka T, Hartmann D, Costa V, Serneels L, Craessaerts K, Metzger K, Frezza C, Annaert W, D'Adamio L, Derks C, Dejaegere T, Pellegrini L, D'Hooge R, Scorrano L, De Strooper B (2006) Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126:163–175

    Article  CAS  PubMed  Google Scholar 

  • Collins Y, Chouchani ET, James AM, Menger KE, Cocheme HM, Murphy MP (2012) Mitochondrial redox signalling at a glance. J Cell Sci 125:801–806

    Article  CAS  PubMed  Google Scholar 

  • Costa V, Giacomello M, Hudec R, Lopreiato R, Ermak G, Lim D, Malorni W, Davies KJ, Carafoli E, Scorrano L (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Croston TL, Thapa D, Holden AA, Tveter KJ, Lewis SE, Shepherd DL, Nichols CE, Long DM, Olfert IM, Jagannathan R, Hollander JM (2014) Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart. Am J Physiol Heart Circ Physiol 307:H54–H65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui M, Tang X, Christian WV, Yoon Y, Tieu K (2010) Perturbations in mitochondrial dynamics induced by human mutant PINK1 can be rescued by the mitochondrial division inhibitor mdivi-1. J Biol Chem 285:11740–11752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dagda RK, Cherra SJ 3rd, Kulich SM, Tandon A, Park D, Chu CT (2009) Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem 284:13843–13855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davies VJ, Hollins AJ, Piechota MJ, Yip W, Davies JR, White KE, Nicols PP, Boulton ME, Votruba M (2007) Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. Hum Mol Genet 16:1307–1318

    Article  CAS  PubMed  Google Scholar 

  • de Brito OM, Scorrano L (2008) Mitofusin 2: a mitochondria-shaping protein with signaling roles beyond fusion. Antioxid Redox Signal 10:621–633

    Article  PubMed  CAS  Google Scholar 

  • Deng H, Dodson MW, Huang H, Guo M (2008) The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A 105:14503–14508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dietrich MO, Liu ZW, Horvath TL (2013) Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell 155:188–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Disatnik MH, Ferreira JC, Campos JC, Gomes KS, Dourado PM, Qi X, Mochly-Rosen D (2013) Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction. J Am Heart Assoc 2, e000461

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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 281:37972–37979

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Elkholi R, Renault TT, Serasinghe MN, Chipuk JE (2014) Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy? Cancer Metab 2:16

    Article  PubMed  PubMed Central  Google Scholar 

  • Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C (2007) Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci 27:12413–12418

    Article  CAS  PubMed  Google Scholar 

  • Ferreira IL, Resende R, Ferreiro E, Rego AC, Pereira CF (2010) Multiple defects in energy metabolism in Alzheimer’s disease. Curr Drug Targets 11:1193–1206

    Article  CAS  PubMed  Google Scholar 

  • Ferreira-da-Silva A, Valacca C, Rios E, Populo H, Soares P, Sobrinho-Simoes M, Scorrano L, Maximo V, Campello S (2015) Mitochondrial dynamics protein Drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration. PLoS One 10, e0122308

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, Scorrano L (2006) OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126:177–189

    Article  CAS  PubMed  Google Scholar 

  • Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK (2011) ER tubules mark sites of mitochondrial division. Science 334:358–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galloway CA, Yoon Y (2013) Mitochondrial morphology in metabolic diseases. Antioxid Redox Signal 19:415–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gan X, Huang S, Wu L, Wang Y, Hu G, Li G, Zhang H, Yu H, Swerdlow RH, Chen JX, Yan SS (2014) Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer’s disease cybrid cell. Biochim Biophys Acta 1842:220–231

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Gawlowski T, Suarez J, Scott B, Torres-Gonzalez M, Wang H, Schwappacher R, Han X, Yates JR 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 19:4861–4870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomez-Lazaro M, Bonekamp NA, Galindo MF, Jordan J, Schrader M (2008) 6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells. Free Radic Biol Med 44:1960–1969

    Article  CAS  PubMed  Google Scholar 

  • Griparic L, Kanazawa T, van der Bliek AM (2007) Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage. J Cell Biol 178:757–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo C, Hildick KL, Luo J, Dearden L, Wilkinson KA, Henley JM (2013) SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia. EMBO J 32:1514–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35:505–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 182:573–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harder Z, Zunino R, McBride H (2004) Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Curr Biol 14:340–345

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Hernandez-Alvarez MI, Paz JC, Sebastian D, Munoz JP, Liesa M, Segales J, Palacin M, Zorzano A (2013) Glucocorticoid modulation of mitochondrial function in hepatoma cells requires the mitochondrial fission protein Drp1. Antioxid Redox Signal 19:366–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirai S (2000) Alzheimer disease: current therapy and future therapeutic strategies. Alzheimer Dis Assoc Disord 14(Suppl 1):S11–S17

    Article  CAS  PubMed  Google Scholar 

  • Hoppins S, Lackner L, Nunnari J (2007) The machines that divide and fuse mitochondria. Annu Rev Biochem 76:751–780

    Article  CAS  PubMed  Google Scholar 

  • Ikeda Y, Sciarretta S, Nagarajan N, Rubattu S, Volpe M, Frati G, Sadoshima J (2014) New insights into the role of mitochondrial dynamics and autophagy during oxidative stress and aging in the heart. Oxid Med Cell Longev 2014:210934

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Inoue-Yamauchi A, Oda H (2012) Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells. Biochem Biophys Res Commun 421:81–85

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • 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 

  • Kageyama Y, Zhang Z, Roda R, Fukaya M, Wakabayashi J, Wakabayashi N, Kensler TW, Reddy PH, Iijima M, Sesaki H (2012) Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol 197:535–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karbowski M, Neutzner A, Youle RJ (2007) The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J Cell Biol 178:71–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kashatus JA, Nascimento A, Myers LJ, Sher A, Byrne FL, Hoehn KL, Counter CM, Kashatus DF (2015) Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. Mol Cell 57:537–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim Y, Park J, Kim S, Song S, Kwon SK, Lee SH, Kitada T, Kim JM, Chung J (2008) PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun 377:975–980

    Article  CAS  PubMed  Google Scholar 

  • Klein CJ, Shi Y, Fecto F, Donaghy M, Nicholson G, McEntagart ME, Crosby AH, Wu Y, Lou H, McEvoy KM, Siddique T, Deng HX, Dyck PJ (2011) TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies. Neurology 76:887–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 

  • 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 47:547–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JY, Kapur M, Li M, Choi MC, Choi S, Kim HJ, Kim I, Lee E, Taylor JP, Yao TP (2014) MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria. J Cell Sci 127:4954–4963

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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:e1000795

    Google Scholar 

  • Li H, Alavian KN, Lazrove E, Mehta N, Jones A, Zhang P, Licznerski P, Graham M, Uo T, Guo J, Rahner C, Duman RS, Morrison RS, Jonas EA (2013) A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nat Cell Biol 15:773–785

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li J, Li Y, Jiao J, Wang J, Li Y, Qin D, Li P (2014) Mitofusin 1 is negatively regulated by microRNA 140 in cardiomyocyte apoptosis. Mol Cell Biol 34:1788–1799

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu T, Yu R, Jin SB, Han L, Lendahl U, Zhao J, Nister M (2013) The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. Exp Cell Res 319:2893–2904

    Article  CAS  PubMed  Google Scholar 

  • Lokireddy S, Wijesoma IW, Teng S, Bonala S, Gluckman PD, McFarlane C, Sharma M, Kambadur R (2012) The ubiquitin ligase Mul1 induces mitophagy in skeletal muscle in response to muscle-wasting stimuli. Cell Metab 16:613–624

    Article  CAS  PubMed  Google Scholar 

  • Loson OC, Song Z, Chen H, Chan DC (2013) Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 24:659–667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 284:22938–22951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makino A, Scott BT, Dillmann WH (2010) Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes. Diabetologia 53:1783–1794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manczak M, Calkins MJ, Reddy PH (2011) Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer’s disease: implications for neuronal damage. Hum Mol Genet 20:2495–2509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin OJ, Lai L, Soundarapandian MM, Leone TC, Zorzano A, Keller MP, Attie AD, Muoio DM, Kelly DP (2014) A role for peroxisome proliferator-activated receptor gamma coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circ Res 114:626–636

    Article  CAS  PubMed  Google Scholar 

  • Mears JA, Lackner LL, Fang S, Ingerman E, Nunnari J, Hinshaw JE (2011) Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nat Struct Mol Biol 18:20–26

    Article  CAS  PubMed  Google Scholar 

  • Mishra P, Carelli V, Manfredi G, Chan DC (2014) Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab 19:630–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30:4232–4240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 7:1019–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niemann A, Ruegg M, La Padula V, Schenone A, Suter U (2005) Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease. J Cell Biol 170:1067–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Niemann A, Wagner KM, Ruegg M, Suter U (2009) GDAP1 mutations differ in their effects on mitochondrial dynamics and apoptosis depending on the mode of inheritance. Neurobiol Dis 36:509–520

    Article  CAS  PubMed  Google Scholar 

  • 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 523:171–176

    Article  CAS  PubMed  Google Scholar 

  • Olichon A, Guillou E, Delettre C, Landes T, Arnaune-Pelloquin L, Emorine LJ, Mils V, Daloyau M, Hamel C, Amati-Bonneau P, Bonneau D, Reynier P, Lenaers G, Belenguer P (2006) Mitochondrial dynamics and disease, OPA1. Biochim Biophys Acta 1763:500–509

    Article  CAS  PubMed  Google Scholar 

  • Olichon A, Elachouri G, Baricault L, Delettre C, Belenguer P, Lenaers G (2007) OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis. Cell Death Differ 14:682–692

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Ong SB, Kalkhoran SB, Cabrera-Fuentes HA, Hausenloy DJ (2015) Mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease. Eur J Pharmacol 763:104–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT (2011) MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep 12:565–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT (2002) Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat Neurosci 5:731–736

    CAS  PubMed  Google Scholar 

  • Papanicolaou KN, Khairallah RJ, Ngoh GA, Chikando A, Luptak I, O’Shea KM, Riley DD, Lugus JJ, Colucci WS, Lederer WJ, Stanley WC, Walsh K (2011) Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol 31:1309–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papanicolaou KN, Ngoh GA, Dabkowski ER, O'Connell KA, Ribeiro RF Jr, Stanley WC, Walsh K (2012) Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death. Am J Physiol Heart Circ Physiol 302:H167–H179

    Article  CAS  PubMed  Google Scholar 

  • Park YY, Cho H (2012) Mitofusin 1 is degraded at G2/M phase through ubiquitylation by MARCH5. Cell Div 7:25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park YY, Lee S, Karbowski M, Neutzner A, Youle RJ, Cho H (2010) Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. J Cell Sci 123:619–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pham AH, Meng S, Chu QN, Chan DC (2012) Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit. Hum Mol Genet 21:4817–4826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pickrell AM, Youle RJ (2015) The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85:257–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, le Huynh H, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F (2012) Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res 94:408–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  PubMed Central  CAS  Google Scholar 

  • Prudent J, Zunino R, Sugiura A, Mattie S, Shore GC, McBride HM (2015) MAPL SUMOylation of Drp1 stabilizes an ER/mitochondrial platform required for cell death. Mol Cell 59:941–955

    Article  CAS  PubMed  Google Scholar 

  • 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 22:256–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian W, Choi S, Gibson GA, Watkins SC, Bakkenist CJ, Van Houten B (2012) Mitochondrial hyperfusion induced by loss of the fission protein Drp1 causes ATM-dependent G2/M arrest and aneuploidy through DNA replication stress. J Cell Sci 125:5745–5757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 108:10190–10195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reddy PH, Reddy TP, Manczak M, Calkins MJ, Shirendeb U, Mao P (2011) Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Res Rev 67:103–118

    Article  CAS  PubMed  Google Scholar 

  • Reddy PH, Tripathi R, Troung Q, Tirumala K, Reddy TP, Anekonda V, Shirendeb UP, Calkins MJ, Reddy AP, Mao P, Manczak M (2012) Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer’s disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim Biophys Acta 1822:639–649

    Article  CAS  PubMed  Google Scholar 

  • Rehman J, Zhang HJ, Toth PT, Zhang Y, Marsboom G, Hong Z, Salgia R, Husain AN, Wietholt C, Archer SL (2012) Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB J 26:2175–2186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Renault TT, Floros KV, Elkholi R, Corrigan KA, Kushnareva Y, Wieder SY, Lindtner C, Serasinghe MN, Asciolla JJ, Buettner C, Newmeyer DD, Chipuk JE (2015) Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis. Mol Cell 57:69–82

    Article  CAS  PubMed  Google Scholar 

  • Rui Y, Tiwari P, Xie Z, Zheng JQ (2006) Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons. J Neurosci 26:10480–10487

    Article  CAS  PubMed  Google Scholar 

  • 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 116:2763–2774

    Article  CAS  PubMed  Google Scholar 

  • Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H (2003) Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria. Biochem Biophys Res Commun 300:482–493

    Article  CAS  PubMed  Google Scholar 

  • Scarpulla RC, Vega RB, Kelly DP (2012) Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab 23:459–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schapira AH (2006) Etiology of Parkinson’s disease. Neurology 66:S10–S23

    Article  PubMed  Google Scholar 

  • Schapira AH, Patel S (2014) Targeting mitochondria for neuroprotection in Parkinson disease. JAMA Neurol 71:537–538

    Article  PubMed  Google Scholar 

  • Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453–R462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneeberger M, Dietrich MO, Sebastian D, Imbernon M, Castano C, Garcia A, Esteban Y, Gonzalez-Franquesa A, Rodriguez IC, Bortolozzi A, Garcia-Roves PM, Gomis R, Nogueiras R, Horvath TL, Zorzano A, Claret M (2013) Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 155:172–187

    Article  CAS  PubMed  Google Scholar 

  • Serasinghe MN, Yoon Y (2008) The mitochondrial outer membrane protein hFis1 regulates mitochondrial morphology and fission through self-interaction. Exp Cell Res 314:3494–3507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serasinghe MN, Seneviratne AM, Smrcka AV, Yoon Y (2010) Identification and characterization of unique proline-rich peptides binding to the mitochondrial fission protein hFis1. J Biol Chem 285:620–630

    Article  CAS  PubMed  Google Scholar 

  • Serasinghe MN, Wieder SY, Renault TT, Elkholi R, Asciolla JJ, Yao JL, Jabado O, Hoehn K, Kageyama Y, Sesaki H, Chipuk JE (2015) Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol Cell 57:521–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, Morrow E, Ryan JJ, Archer SL (2014) Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J 28:316–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirendeb U, Reddy AP, Manczak M, Calkins MJ, Mao P, Tagle DA, Reddy PH (2011) Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington’s disease: implications for selective neuronal damage. Hum Mol Genet 20:1438–1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirendeb UP, Calkins MJ, Manczak M, Anekonda V, Dufour B, McBride JL, Mao P, Reddy PH (2012) Mutant huntingtin’s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington’s disease. Hum Mol Genet 21:406–420

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y, Poquiz P, Tjong J, Pouladi MA, Hayden MR, Masliah E, Ellisman M, Rouiller I, Schwarzenbacher R, Bossy B, Perkins G, Bossy-Wetzel E (2011) Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med 17:377–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sorianello E, Soriano FX, Fernandez-Pascual S, Sancho A, Naon D, Vila-Caballer M, Gonzalez-Navarro H, Portugal J, Andres V, Palacin M, Zorzano A (2012) The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells. Cardiovasc Res 94:38–47

    Article  CAS  PubMed  Google Scholar 

  • 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 55:1783–1791

    Article  CAS  PubMed  Google Scholar 

  • Sugiura A, Nagashima S, Tokuyama T, Amo T, Matsuki Y, Ishido S, Kudo Y, McBride HM, Fukuda T, Matsushita N, Inatome R, Yanagi S (2013) MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. Mol Cell 51:20–34

    Article  CAS  PubMed  Google Scholar 

  • Supnet C, Bezprozvanny I (2010) Neuronal calcium signaling, mitochondrial dysfunction, and Alzheimer’s disease. J Alzheimers Dis 20(Suppl 2):S487–S498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tabrizi SJ, Cleeter MW, Xuereb J, Taanman JW, Cooper JM, Schapira AH (1999) Biochemical abnormalities and excitotoxicity in Huntington’s disease brain. Ann Neurol 45:25–32

    Article  CAS  PubMed  Google Scholar 

  • 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 282:11521–11529

    Article  CAS  PubMed  Google Scholar 

  • Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ (2010) Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 191:1367–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trudeau K, Molina AJ, Guo W, Roy S (2010) High glucose disrupts mitochondrial morphology in retinal endothelial cells: implications for diabetic retinopathy. Am J Pathol 177:447–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160

    Article  CAS  PubMed  Google Scholar 

  • Wai T, Garcia-Prieto J, Baker MJ, Merkwirth C, Benit P, Rustin P, Ruperez FJ, Barbas C, Ibanez B, Langer T (2015) Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science 350, aad0116

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi J, Zhang Z, Wakabayashi N, Tamura Y, Fukaya M, Kensler TW, Iijima M, Sesaki H (2009) The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol 186:805–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh C, Barrow S, Voronina S, Chvanov M, Petersen OH, Tepikin A (2009) Modulation of calcium signalling by mitochondria. Biochim Biophys Acta 1787:1374–1382

    Article  CAS  PubMed  Google Scholar 

  • Wang CE, Tydlacka S, Orr AL, Yang SH, Graham RK, Hayden MR, Li S, Chan AW, Li XJ (2008a) Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntington’s disease. Hum Mol Genet 17:2738–2751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X (2008b) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci U S A 105:19318–19323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Lim PJ, Karbowski M, Monteiro MJ (2009a) Effects of overexpression of huntingtin proteins on mitochondrial integrity. Hum Mol Genet 18:737–752

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009b) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 29:9090–9103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Song P, Du L, Tian W, Yue W, Liu M, Li D, Wang B, Zhu Y, Cao C, Zhou J, Chen Q (2011) Parkin ubiquitinates Drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in Parkinson disease. J Biol Chem 286:11649–11658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 15:186–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ward PS, Thompson CB (2012a) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21:297–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ward PS, Thompson CB (2012b) Signaling in control of cell growth and metabolism. Cold Spring Harb Perspect Biol 4:a006783

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wasiak S, Zunino R, McBride HM (2007) Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 177:439–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV (2007) A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 356:1736–1741

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Wieder SY, Serasinghe MN, Sung JC, Choi DC, Birge MB, Yao JL, Bernstein E, Celebi JT, Chipuk JE (2015) Activation of the mitochondrial fragmentation protein DRP1 correlates with BRAF(V600E) melanoma. J Invest Dermatol 135:2544–2547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams PA, Morgan JE, Votruba M (2010) Opa1 deficiency in a mouse model of dominant optic atrophy leads to retinal ganglion cell dendropathy. Brain 133:2942–2951

    Article  PubMed  Google Scholar 

  • Williams PA, Morgan JE, Votruba M (2011) Mouse models of dominant optic atrophy: what do they tell us about the pathophysiology of visual loss? Vision Res 51:229–234

    Article  CAS  PubMed  Google Scholar 

  • Williams PA, Piechota M, von Ruhland C, Taylor E, Morgan JE, Votruba M (2012) Opa1 is essential for retinal ganglion cell synaptic architecture and connectivity. Brain 135:493–505

    Article  PubMed  Google Scholar 

  • Xie Q, Wu Q, Horbinski CM, Flavahan WA, Yang K, Zhou W, Dombrowski SM, Huang Z, Fang X, Shi Y, Ferguson AN, Kashatus DF, Bao S, Rich JN (2015) Mitochondrial control by DRP1 in brain tumor initiating cells. Nat Neurosci 18:501–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 25:3618–3626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Yu T, Robotham JL, Yoon Y (2006) Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci U S A 103:2653–2658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 14:425–437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yue W, Chen Z, Liu H, Yan C, Chen M, Feng D, Yan C, Wu H, Du L, Wang Y, Liu J, Huang X, Xia L, Liu L, Wang X, Jin H, Wang J, Song Z, Hao X, Chen Q (2014) A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30. Cell Res 24:482–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Z, Kageyama Y, Sesaki H (2012) Mitochondrial division prevents neurodegeneration. Autophagy 8:1531–1533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Liu T, Jin S, Wang X, Qu M, Uhlen P, Tomilin N, Shupliakov O, Lendahl U, Nister M (2011) Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission. EMBO J 30:2762–2778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Zhang J, Yu M, Xie Y, Huang Y, Wolff DW, Abel PW, Tu Y (2013) Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene 32:4814–4824

    Article  CAS  PubMed  Google Scholar 

  • Ziviani E, Whitworth AJ (2010) How could Parkin-mediated ubiquitination of mitofusin promote mitophagy? Autophagy 6:660–662

    Article  PubMed  PubMed Central  Google Scholar 

  • Zuchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, Hamilton SR, Van Stavern G, Krajewski KM, Stajich J, Tournev I, Verhoeven K, Langerhorst CT, de Visser M, Baas F, Bird T, Timmerman V, Shy M, Vance JM (2006) Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol 59:276–281

    Article  CAS  PubMed  Google Scholar 

  • 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 120:1178–1188

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy PLC, New York, NY, 10029, USA

    Madhavika N. Serasinghe & Jerry E. Chipuk

Authors
  1. Madhavika N. Serasinghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jerry E. Chipuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Madhavika N. Serasinghe .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Harpreet Singh

  2. Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Shey-Shing Sheu

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Serasinghe, M.N., Chipuk, J.E. (2016). Mitochondrial Fission in Human Diseases. In: Singh, H., Sheu, SS. (eds) Pharmacology of Mitochondria. Handbook of Experimental Pharmacology, vol 240. Springer, Cham. https://doi.org/10.1007/164_2016_38

Download citation

Publish with us

Policies and ethics

Search

Navigation