Skip to main content
SpringerLink
Log in

Mitochondrial Diseases as Model of Neurodegeneration

  • Chapter
  • First Online:
Personalised Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1007))

Abstract

“Mitochondria” partially autonomous sophisticated cellular organelle involved in a wide range of crucial cellular functions, well known as the power house of the cell where ATP (adenosine triphosphate) production takes place, that is the cellular source of energy.

Mitochondria has its own genome, however proper functioning of the mitochondria is dependent upon the coordinated expression of both nuclear and mitochondrial encoded gene products. Peculiar maternal inheritance of mitochondrial DNA has led the scientists to think about mitochondrial donation as a solution to maternally inherited mitochondriopathy “Three parent baby”, raising many ethical and scientific issues, concerns about safety of the procedure, long term outcome and effect of genetic modification are still questionable.

Mitochondrial DNA has a higher mutation rate compared to nuclear DNA. Mitochondrial research has revealed a lot about methods of its DNA repair emphasizing the role of nuclear encoded products in this process.

Mitochondrial diseases are clinically and genetically diverse, fortunately next generation sequencing (NGS) technologies have made a breakthrough in mitochondrial disorders, the whole mitochondrial genome has been sequenced with more than 250 nuclear encoded genes associated with mitochondrial syndromes identified to date, It unraveled the role of mitochondrial disorders in neurodegenerative disorders. However many pathogenic candidate genes remain uncharacterized even with whole exome sequencing (WES).

In this chapter here we handle cases with various neurodegenerative diseases that have been genetically diagnosed thanks to NGS, revealing the role of mitochondrial dysfunction in neurodegeneration, offering a therapeutic target for these handicapping disorders.

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 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
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

  1. “Mitochondria”. Online Etymology Dictionary

    Google Scholar 

  2. Duchen MR (2004) Mitochondria in health and disease: perspectives on a new mitochondrial biology, Mol Asp Med, vol. 25 (pg. 365–351)

    Google Scholar 

  3. Koopman WJH, Willems PHGM, Smeitink JAM (2012) Monogenic mitochondrial disorders. N Engl J Med 366:1132–1141

    Article  CAS  PubMed  Google Scholar 

  4. Carroll J, Fearnley IM, Skehel JM, Shannon RJ, Hirst J, Walker JE (2006) Bovine complex I is a complex of 45 different subunits. J Biol Chem 281:32724–32727

    Article  CAS  PubMed  Google Scholar 

  5. Kühlbrandt W (2015) Structure and function of mitochondrial membrane protein complexes. BMC Biol 13:89

    Article  PubMed  PubMed Central  Google Scholar 

  6. Available at http://cellpics.cimr.cam.ac.uk/mitochondria.html

  7. Karbowski M (2010) Mitochondria on guard: role of mitochondrial fusion and fission in the regulation of apoptosis. Adv Exp Med Biol 687:131–142

    Article  CAS  PubMed  Google Scholar 

  8. Desler C, Marcker ML, Singh KK, Rasmussen LJ (2011) The importance of mitochondrial DNA in aging and cancer. J Aging Res 2011: 407536-9

    Google Scholar 

  9. Chial H, Craig J (2008) mtDNA and mitochondrial diseases. Nat Educ 1(1):217

    Google Scholar 

  10. Kudryavtseva AV, Krasnov GS, Dmitriev AA, Alekseev BY, Kardymon OL, Sadritdinova AF, Fedorova MS, Pokrovsky AV, Melnikova NV, Kaprin AD, Moskalev AA, Snezhkina AV (2016) Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget 7(29):44879–44905

    Google Scholar 

  11. Mohamed Yusoff AA (2015) Role of mitochondrial DNA mutations in brain tumors: a mini-review. J Cancer Res Ther 11(3):535–544

    Article  PubMed  Google Scholar 

  12. Sazanov LA (2015) Giant molecular proton pump: structure and mechanism of respiratory complex I. Nat Rev Mol Cell Biol 16(6):375–388

    Google Scholar 

  13. Koopman WJH, Distelmaier F, Smeitink JAM,Willems PHGM (2013) OXPHOS mutations and neurodegeneration. EMBO J 32(1):9–29

    Google Scholar 

  14. Available at https://biochemist01.wordpress.com/tag/electron-transport-chain/

  15. Distelmaier F, Koopman WJ, van den Heuvel LP, Rodenburg RJ, Mayatepek E, Willems PH, Smeitink JA (2009) Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain 132(Pt 4):833–842. doi:10.1093/brain/awp058

    PubMed  Google Scholar 

  16. Alston CL, Compton AG, Formosa LE, Strecker V, Oláhová M, Haack TB, Smet J, Stouffs K, Diakumis P, Ciara E, Cassiman D, Romain N, Yarham JW, He L, De Paepe B, Vanlander AV6, Seneca S, Feichtinger RG, Płoski R, Rokicki D, Pronicka E, Haller RG, Van Hove JL, Bahlo M, Mayr JA, Van Coster R, Prokisch H, Wittig I, Ryan MT, Thorburn DR, Taylor RW (2016) Biallelic mutations in TMEM126B cause severe complex I deficiency with a variable clinical phenotype. Am J Hum Genet 99(1):217–227

    Google Scholar 

  17. Belevich I, Verkhovsky MI, Wikström M (2006) Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase. Nature 440:829–832

    Article  CAS  PubMed  Google Scholar 

  18. Mick DU, Fox TD, Rehling P (2011) Inventory control: cytochrome c oxidase assembly regulates mitochondrial translation. Nat Rev Mol Cell Biol 12:14–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Balsa E, Marco R, Perales-Clemente E et al (2012) NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab 16:378–386

    Article  CAS  PubMed  Google Scholar 

  20. Oláhová M, Haack TB, Alston CL, Houghton JA, He L, Morris AA, Brown GK, McFarland R, Chrzanowska-Lightowlers ZM, Lightowlers RN, Prokisch H, Taylor RW (2015) A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency. Eur J Hum Genet 23(7):935–939

    Google Scholar 

  21. Sharma LK, Lu J, Bai Y (2009) Mitochondrial respiratory complex I: structure, function and implication in human diseases. Curr Med Chem 16(10):1266–1277

    Google Scholar 

  22. Castellana S, Vicario S, Saccone C (2011) Evolutionary patterns of the mitochondrial genome in Metazoa: exploring the role of mutation and selection in mitochondrial protein–coding genes. Genome Biol Evol 3:1067–1079

    Article  CAS  PubMed Central  Google Scholar 

  23. Chan DC, Schon EA (2012) Eliminating mitochondrial DNA from sperm. Dev Cell 22(3):469–470

    Google Scholar 

  24. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134:112–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kliegman R, Stanton B, Geme JS, Schor NF (2016) Nelson textbook of Pediatrics, 20th edn.1600 John F.Kennedy Blvd, Ste. 1800. Elsevier

    Google Scholar 

  26. Available at TutorVista.Com

    Google Scholar 

  27. Available at WWW.slide share.Net%2FAmeena1994%2F–mitochondrial-DNA-mutation

  28. Nadia R Mitochondrial diseases: the cracked bottleneck of inheritance. J Young Investig. Retrieved from http://www.jyi.org/issue/mitochondrial-diseases-the-cracked-bottleneck-of-inheritance/

  29. Amato P, Tachibana M, Sparman M, Mitalipov S (2014) Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril 101(1):31–35

    Google Scholar 

  30. Meyers DE, Basha HI, Mary Kay Koenig MK (2013) Mitochondrial cardiomyopathy pathophysiology, diagnosis, and management. Tex Heart Inst J 40(4): 385–394

    Google Scholar 

  31. DiMauro S (2011) A history of mitochondrial diseases. J Inherit Metab Dis 34:261–276

    Article  CAS  PubMed  Google Scholar 

  32. Debray FG, Lambert M, Mitchell GA (2008) Disorders of mitochondrial function. Curr Opin Pediatr 20:471–482

    Article  PubMed  Google Scholar 

  33. Pitceathly RDS, Smith C, Fratter C, Alston CL, He LP, Craig K, Blakely EL, Evans JC, Taylor J, Shabbir Z et al (2012) Adults with RRM2B-related mitochondrial disease have distinct clinical and molecular characteristics. Brain 135:3392–3403

    Article  PubMed  PubMed Central  Google Scholar 

  34. Suomalainen A, Isohanni P (2010) Mitochondrial DNA depletion syndromes—many genes, common mechanisms. Neuromuscul Disord 20:429–437

    Article  PubMed  Google Scholar 

  35. Mayr JA, Haack TB, Freisinger P et al (2015) Spectrum of combined respiratory chain defects. J Inherit Metab Dis 38(4):629–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chatterjee A, Mambo E, Sidransky D (2006) Mitochondrial DNA mutations in human cancer. Oncogene 25:4663–4674

    Article  CAS  PubMed  Google Scholar 

  37. Janssen RJ, Nijtmans LG, van den Heuvel LP, Smeitink JA (2006) Mitochondrial complex I: structure, function and pathology. J Inherit Metab Dis 29:499–515

    Article  CAS  PubMed  Google Scholar 

  38. Oláhová M, Thompson K, Hardy SA, Barbosa IA, Besse A, Anagnostou ME, White K, Davey T, Simpson MA, Champion M, Enns G, Schelley S, Lightowlers RN, Chrzanowska-Lightowlers ZM1, McFarland R, Deshpande C, Bonnen PE, Taylor RW (2017) Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria. J Inherit Metab Dis 40(1):121–130

    Google Scholar 

  39. Forster K (2016) Three-person IVF can prevent babies from inheriting deadly genetic diseases. Indepenent. Retrieved from http://www.independent.co.uk/life-style/health-and-families/health-news/three-parent-baby-hfea-allowed-technique-birth-child-ruling-fertility-decision-a7476731.html

  40. Palacios-González C (2016) Mitochondrial replacement techniques: egg donation, genealogy and eugenics. 1-Monash Bioeth Rev 34(1):37–51

    Google Scholar 

  41. Tibbitts T (2014) Third scientific review of the safety and efficacy of methods to avoid mitochondrial disease through assisted conception, human fertilisation and embryology authority

    Google Scholar 

  42. Reardon S. Genetic controversial of three parent baby revealed but the child’s parents have decided to forego long-term monitoring by researchers. Nat Int Weakly J Sci. Retrieved from https://www.nature.com/news/genetic-details-of-controversial-three-parent-baby-revealed-1.21761

  43. Coghlan A (2016) ‘3-parent’ baby method already used for infertility. New scientist. Retrieved from https://www.newscientist.com/article/2108549-exclusive-3-parent-baby-method-already-used-for-infertility/

  44. Scutti S (2017) Controversial IVF technique produces a baby girl -- and for some, that’s a problem. CNN. Retrieved from http://edition.cnn.com/2017/01/18/health/ivf-three-parent-baby-girl-ukraine-bn/

  45. Chiang SC, Meagher M, Kassouf N, Hafezparast M, McKinnon PJ, Haywood R, El-Khamisy SF (2017) Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage. Sci Adv 3(4):e1602506. doi: 10.1126/sciadv.1602506. eCollection 2017

  46. Bianchi NO, Bianchi MS, Richard SM (2001) Mitochondrial genome instability in human cancers. Mutat Res 488(1):9–23

    Google Scholar 

  47. Kazak L, Reyes A, Holt IJ (2012) Minimizing the damage: repair pathways keep mitochondrial DNA intact. Nat Rev Mol Cell Biol 13(10):659–671

    Google Scholar 

  48. Richard SM, Bailliet G, Páez GL, Bianchi MS, Peltomäki P, Bianchi NO (2000) Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res 60(15):4231–4237

    Google Scholar 

  49. WIand S, Yorek MA (2010) Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal 12(4):537–577

    Google Scholar 

  50. Krssak M, Petersen KF, Dresner A et al (1999) Intramyocellular lipid concentrations are correlated with insulin sensitivity in man: a 1H NMR spectroscopy study. Diabetologia 41:113–116

    Article  Google Scholar 

  51. Kirches E (2011) LHON: mitochondrial mutations and more. Curr Genomics 12:44–54

    Google Scholar 

  52. Chen H, Chan DC (2005) Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14:283–289

    Article  Google Scholar 

  53. Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferré M, Guillet V, Gueguen N, Loiseau D, de Crescenzo MA, Verny C, Procaccio V, Lenaers G, Reynier P (2009) OPA1-associated disorders: phenotypes and pathophysiology. Int J Biochem Cell Biol 41(10):1855–1865. doi: 10.1016/j.biocel.2009.04.012. Epub Apr 21. Review

  54. Cohn AC, Toomes C, Hewitt AW, Kearns LS, Inglehearn CF, Craig JE, Mackey DA (2007) The natural history of OPA1-related autosomal dominant optic atrophy. Br J Ophthalmol 92(10):1333–1336. doi: 10.1136/bjo.134726

  55. Zanna C, Ghelli A, Porcelli AM, Karbowski M, Youle RJ, Schimpf S, Wissinger B, Pinti M, Cossarizza A, Vidoni S, Valentino ML, Rugolo M, Carelli V (2008) OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131(Pt 2):352–367. doi: 10.1093/brain/awm335

  56. Available at emedicine. medscape.com/article1217760-overview

  57. Federico A, et al (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci

    Google Scholar 

  58. 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(12):4232–4240

    Google Scholar 

  59. Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, et al. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36:449–451

    Google Scholar 

  60. Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, et al. (2005) The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet 14:1405–1415

    Google Scholar 

  61. Funalot B, Magdelaine C, Sturtz F, Ouvrier R, Vallat JM (2009) Ultrastructural lesions of axonal mitochondria in patients with childhood-onset Charcot-Marie-Tooth disease due to MFN2 mutations. Bull Acad Natl Med 193:151–60

    Google Scholar 

  62. Rouzier C, Bannwarth S, Chaussenot A, Chevrollier A, Verschueren A, Bonello-Palot N et al (2012) The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy ‘plus’ phenotype. Brain 135:23–34

    Article  PubMed  Google Scholar 

  63. Loiseau D, Chevrollier A, Verny C, Guillet V, Gueguen N, Pou de Crescenzo MA et al (2007) Mitochondrial coupling defect in Charcot-Marie-tooth type 2A disease. Ann Neurol 61:315–323

    Article  CAS  PubMed  Google Scholar 

  64. Hirano M, DiMauro S (1996) Clinical features of mitochondrial myopathies and encephalomyopathies. In: Lane RJM (ed) Handbook of muscle disease. Marcel Dekker Inc, New York, pp 479–504

    Google Scholar 

  65. Wahbi K, Larue S, Jardel C, Meune C, Stojkovic T, Ziegler F, Lombes A, Eymard B, Duboc D, Laforet P (2010) Cardiac involvement is frequent in patients with the m.8344A>G mutation of mitochondrial DNA. Neurology 74:674–677

    Article  CAS  PubMed  Google Scholar 

  66. Greaves LC, Reeve AK, Taylor RW, Turnbull DM (2012) Mitochondrial DNA and disease. J Pathol 226:274–286

    Article  CAS  PubMed  Google Scholar 

  67. Rommelaere G, Michel S, Malaisse J, Charlier S, Arnould T, Renard P (2012) Hypersensitivity of A8344G MERRF mutated cybrid cells to staurosporine-induced cell death is mediated by calcium-dependent activation of calpains. Int J Biochem Cell Biol 44:139–149

    Article  CAS  PubMed  Google Scholar 

  68. Quinzii CM, Hirano M (2011) Primary and secondary CoQ(10) deficiencies in humans. Biofactors 37:361–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Montero R, Pineda M, Aracil A, Vilaseca MA, Briones P, Sánchez-Alcázar JA et al (2007) Clinical, biochemical and molecular aspects of cerebellar ataxia and coenzyme Q10 deficiency. Cerebellum 6:118–122

    Article  CAS  PubMed  Google Scholar 

  70. Boitier E, Degoul F, Desguerre I, Charpentier C, François D et al (1998) A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency. J Neurol Sci 156:41–46

    Article  CAS  PubMed  Google Scholar 

  71. Di Giovanni S, Mirabella M, Spinazzola A, Crociani P, Silvestri G et al (2001) Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 57:515–518

    Article  PubMed  Google Scholar 

  72. Dinwiddie DL, Smith LD, Miller NA, Atherton AM, Farrow EG et al (2013) Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome. Genomics 102:148–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Jakobs BS, van den Heuvel LP, Smeets RJ, de Vries MC, Hien S et al (2013) A novel mutation in COQ2 leading to fatal infantile multisystem disease. J Neurol Sci 326:24–28

    Article  CAS  PubMed  Google Scholar 

  74. Scalais E, Chafai R, Van Coster R, Bindl L, Nuttin C, et al. (2013) Early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome in a patient with CoQ10 deficiency caused by mutations in para-hydroxybenzoate-polyprenyl transferase (COQ2). Eur J Paediatr Neurol 17:625–630

    Google Scholar 

  75. Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V et al (2013) ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J Clin Invest 123:5179–5189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. McCarthy HJ, Bierzynska A, Wherlock M, Ognjanovic M, Kerecuk L et al (2013) Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 8:637–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ et al (2011) COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J Clin Invest 121:2013–2024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Horvath R (2012) Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ10). J Inherit Metab Dis 35:679–687

    Google Scholar 

  79. Liu YT, Hersheson J, Plagnol V, Fawcett K, Duberley KE et al (2013) Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation. J Neurol Neurosurg Psychiatry

    Google Scholar 

  80. Mignot C, Apartis E, Durr A, Marques Lourenço C et al (2013) Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression. Orphanet J Rare Dis 8:173

    Article  PubMed  PubMed Central  Google Scholar 

  81. Horvath R, Schneiderat P, Schoser BG, Gempel K, Neuen-Jacob E et al (2006) Coenzyme Q10 deficiency and isolated myopathy. Neurology 66:253–255

    Article  CAS  PubMed  Google Scholar 

  82. Gempel K, Topaloglu H, Talim B, Schneiderat P, Schoser BG et al (2007) The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene. Brain 130:2037–2044

    Article  PubMed  PubMed Central  Google Scholar 

  83. Copeland WC (2008) Inherited mitochondrial diseases of DNA replication. Annu Rev Med 59:131–146. pmid:17892433

    Google Scholar 

  84. Nguyen KV, Ostergaard E, Ravn SH, Balslev T, Danielsen ER, Vardag A et al (2005) POLG mutations in Alpers syndrome. Neurology 65:1493–1495

    Article  CAS  PubMed  Google Scholar 

  85. Hudson G, Chinnery PF (2006) Mitochondrial DNA polymerase-gamma and human disease. Hum Mol Genet 2:244–252

    Google Scholar 

  86. Luoma PT, Eerola J, Ahola S, Hakonen AH, Hellström O, Kivistö KT et al (2007) Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology 69:1152–1159

    Article  CAS  PubMed  Google Scholar 

  87. Eerola J, Luoma PT, Peuralinna T, Scholz S, Paisan-Ruiz C, Suomalainen A et al (2010) POLG1 polyglutamine tract variants associated with Parkinson’s disease. Neurosci Lett 477:1–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Anvret A, Westerlund M, Sydow O, Willows T, Lind C, Galter D et al (2010) Variations of the CAG trinucleotide repeat in DNA polymerase γ (POLG1) is associated with Parkinson’s disease in Sweden. Neurosci Lett 485:117–120

    Article  CAS  PubMed  Google Scholar 

  89. Mancuso M, Filosto M, Orsucci D, Siciliano G (2008) Mitochondrial DNA sequence variation and neurodegeneration. Hum Genomics 3:71–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Seidowsky A, Hoffmann M, Glowacki F, Dhaenens CM, Devaux JP, Lessore de Sainte Foy C, et al (2012) Renal involvement in MELAS syndrome - a series of 5 cases and review of the literature. Clin Nephrol

    Google Scholar 

  91. Meseguer S, Martínez-Zamora A, García-Arumí E, Andreu AL, Armengod ME (2014) The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial tRNA-modifying enzymes and is involved in the molecular mechanism of MELAS syndrome. Hum Mol Genet

    Google Scholar 

  92. Testai FD, Gorelick PB (2010) Inherited metabolic disorders and stroke part 1: Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Arch Neurol 67(1):19–24

    Article  PubMed  Google Scholar 

  93. Liu K, Zhao H, Ji K, Yan C (2014) MERRF/MELAS overlap syndrome due to the m.3291T>C mutation. Metab Brain Dis 29(1):139–144

    Article  CAS  PubMed  Google Scholar 

  94. Sasarman F, Antonicka H, Shoubridge EA (2008) The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2. Hum Mol Genet 17(23):3697–3707

    Article  CAS  PubMed  Google Scholar 

  95. Selim L, Mehany D (2013) Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes in a Japanese child: clinical, radiological and molecular genetic analysis. The Egy J Med H Gen 14:317–322

    Article  Google Scholar 

  96. Hirano M, MARTI R, Spinazzola A, Nishinol, Nishigaki Y (2004) Thymidine phosphorylase deficiency causes MNGIE: an autosomal recessive mitochondrial disorder. Nucleosides Nucleotides Nucleic Acids 23:1217–1225

    Google Scholar 

  97. Garone C, Tadesse S, Hirano M (2011) Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. Brain 134:3326–3332

    Article  PubMed  PubMed Central  Google Scholar 

  98. Said G, Lacroix C, Plante-Bordeneuveu, Messing B, Slama A, Crenn P, Nivelon Chevallier A, Bedenne L, Soichot P, Manceau E, Rigaud D, Guiochon-Mantel A, Matuchansky C (2005) Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation. J Neurol 252:655–662

    Article  PubMed  Google Scholar 

  99. Van Goethem G, Schwartz M, LÖfrena, Dermaut B, Van Van Broeckhoven C, Vissing J (2003) Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. Eur J Hum Genet, 11:547–549

    Google Scholar 

  100. Slama A, Lacroix C, Plante-Bordeneuve V, Lombès A, Conti M, Reimund JM, Auxenfants E, Crenn P, Laforêt P, Joannard A, Seguy D, Pillant H, Joly P, Haut S, Messing B, Said G, Legrand A, Guiochon-Mantel A (2005) Thymidine phosphorylase gene mutations in patients with mitochondrial neurogastrointestinal encephalomyopathy syndrome. Mol Genet Meta 84:326–331

    Article  CAS  Google Scholar 

  101. Selim L, Van Coster R, Mehaney D, Hassan F, Vanlander A, Smet J, De Latter E, VAndemeulebroecke K, Mohamed Abdou D, Nakhla G, Mostafa M, Habets D, Bakker J, Abdel Elbary A (2016) Mitochondrial neurogastrointestinal encephalopathy; clinical, biochemical and molecular study in three Egyptian patients. Genetic Counselling 2:193–205

    Google Scholar 

  102. Exner N, Lutz AK, Haass C, Winklhofer KF (2012) Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J 31:3038–3062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4:600–609

    Article  CAS  PubMed  Google Scholar 

  104. Swerdlow RH (2009) The neurodegenerative mitochondriopathies. J Alzheimers Dis 17:737–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38:518–520

    Article  CAS  PubMed  Google Scholar 

  106. Winklhofer KF, Haass C (2010) Mitochondrial dysfunction in Parkinson’s disease. Biochimica et Biophysica Acta (BBA) – Mol Basis Dis 1802(1):29–44

    Google Scholar 

  107. Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK (2008) Mitochondrial import and accumulation of α-Synuclein impair complex I in human Dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem 283(14):9089–9100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Song DD, Shults CW, Sisk A, Rockenstein E, Masliah E (2004) Enhanced substantia nigra mitochondrial pathology in human α-synuclein transgenic mice after treatment with MPTP. Exp Neurol 186:158–172

    Google Scholar 

  109. Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA et al (2006) Parkinson’s disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci 26:41–50

    Article  CAS  PubMed  Google Scholar 

  110. Flower TR, Chesnokova LS, Froelich CA, Dixon C, Witt SN (2005) Heat shock prevents alpha-synuclein-induced apoptosis in a yeast model of Parkinson’s disease. J Mol Biol 351:1081–1100

    Article  CAS  PubMed  Google Scholar 

  111. Battisti C, Formichi P, Radi E, Federico A (2008) Oxidative-stress-induced apoptosis in PBLs of two patients with Parkinson disease secondary to alpha-synuclein mutation. J Neurol Sci 267:120–124

    Article  CAS  PubMed  Google Scholar 

  112. Abou-Sleiman PM, Muqit MM, Wood NW (2006) Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat Rev Neurosci 7:207–219

    Google Scholar 

  113. Chaturvedi RK, Beal MF (2013) Mitochondria targeted therapeutic approaches in Parkinson’s and Huntington’s diseases. Mol Cell Neurosci 55:101–114

    Article  CAS  PubMed  Google Scholar 

  114. Blakely E, He L, Gardner JL, Hudson G, Walter J, Hughes I et al (2008) Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy. Neuromuscul Disord 18(7):557–560

    Article  PubMed  Google Scholar 

  115. Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E et al (1991) MtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet 48(3):492–501

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Mancuso M, Salviati L, Sacconi S, Otaegui D, Camano P, Marana A et al (2002) Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. Neurology 59:1197–1202

    Article  CAS  PubMed  Google Scholar 

  117. Johansson K, Ramaswamy S, Ljungcrantz C, Knecht W, Piskur J, Munch-Petersen B et al (2001) Structural basis for substrate specificities of cellular deoxyribonucleoside kinases. Nat Struct Biol 8:616–620

    Article  CAS  PubMed  Google Scholar 

  118. Selim L, Mehaney D, Hassan F, Sabry R, Zeyada R, Hassan S, Gamal Eldin I, Bertini E (2012) Mitochondrial DNA depletion syndrome presenting with ataxia and external ophthalmoplegia: case report Egy J Med H n13:351–357

    Google Scholar 

Download references

Acknowledgment

Centogene, Rostock, Germany for performing whole exome sequencing free of charge.

Author information

Authors and Affiliations

  1. Kasr Al Ainy School of Medicine, Cairo University Children Hospital, Cairo, Egypt

    Laila A. Selim & Heba Hassaan

Authors
  1. Laila A. Selim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heba Hassaan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laila A. Selim .

Editor information

Editors and Affiliations

  1. Krebs Institute and Sheffield Institute for Nucleic Acids, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, Sheffield, United Kingdom

    Sherif El-Khamisy

Rights and permissions

Reprints and permissions

Copyright information

© 2017 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Selim, L.A., Hassaan, H. (2017). Mitochondrial Diseases as Model of Neurodegeneration. In: El-Khamisy, S. (eds) Personalised Medicine. Advances in Experimental Medicine and Biology, vol 1007. Springer, Cham. https://doi.org/10.1007/978-3-319-60733-7_8

Download citation

Publish with us

Policies and ethics

Search

Navigation