Mitochondria and Mitochondrial Disorders

  • Marjo S. van der Knaap
  • Jacob Valk


Mitochondria are membranous organelles that are responsible for providing most of the energy required for the cell in the form of adenosine triphosphate (ATP). They are termed mitochondria because of their threadlike appearance (mitos= thread) on light microscopy. On electron microscopy they appear as vesicles bounded by two membranes. The inner membrane is thrown into folds that project like shelves into the mitochondria. These projections are called cristae. Mitochondria consist of four compartments: the outer membrane, the intermembrane space, the inner membrane and the mitochondrial matrix. Mitochondria vary considerably in size in any one cell type, but most have a diameter of between 0.1 and 1.0 µm. In different cell types the size, shape, and number of cristae vary considerably. Most cells contain many mitochondria, the actual number differing in relation to the energy requirements of the type of cell. Mitochondria undergo continual renewal; they divide by fission.


Flavine Adenine Dinucleotide Citric Acid Cycle Intermembrane Space Mitochondrial Disorder Pyruvate Dehydrogenase Complex 
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  1. Agsteribbe E, Huckriede A, Veenhuis M, Ruiters MHJ, NiezenKoning KE, Skjeldal OH, Skullerud K, Gupta RS, Hallberg R, Van Diggelen OP, Scholte HR (1993) A fatal, systemic mitochondrial disease with decreased mitochondrial enzyme activities, abnormal ultrastructure of the mitochondria and deficiency of heat shock protein 60. Biochem Biophys Res Commun 1: 146–154CrossRefGoogle Scholar
  2. Attardi G, Schatz G (1988) Biogenesis of mitochondria. Ann Rev Cell Biol 4: 289–333PubMedCrossRefGoogle Scholar
  3. Benz R (1990) Biophysical properties of porin pores from mitochondrial outer membrane of eukaryotic cells. Experientia 46: 131–137PubMedCrossRefGoogle Scholar
  4. Bowling AC, Mutisya EM, Walker LC, Price DL, Cork LC, Flint Beal M (1993) Age-dependent impairment of mitochondrial function in primate brain. J Neurochem 60: 1964–1967PubMedCrossRefGoogle Scholar
  5. Breningstall GN (1993) Approach to diagnosis of oxidative metabolism disorders. Pediatr Neurol 9: 81–90PubMedCrossRefGoogle Scholar
  6. Cheng MY, Ulrich Hartl F, Martin J, Pollock RA, Kalousek F, Neupert W, Hallberg EM, Hallberg RL, Horwich AL (1989) Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337: 620–625PubMedCrossRefGoogle Scholar
  7. Clayton DA (1992) Structure and function of the mitochondrial genome. J Inherited Metab Dis 15: 439–447PubMedCrossRefGoogle Scholar
  8. Coates PM, Tanaka K (1992) Molecular basis of mitochondrial fatty acid oxidation defects. J Lipid Res 33: 1099–1110PubMedGoogle Scholar
  9. Cote C, Boulet D, Poirier J (1990) Expression of the mammalian mitochondrial genome. J Biol Chem 265: 7532–7538PubMedGoogle Scholar
  10. Crimmins D, Morris JGL, Walker GL, Sue CM, Byrne E, Stevens S, Jean-Francis B, Yiannikas C, Pamphlett R (1993) Mitochondrial encephalomyopathy: variable clinical expression within a single kindred. J Neurol Neurosurg Psychiatry 56: 900–905PubMedCrossRefGoogle Scholar
  11. Cuezva JM, Flores AI, Liras A, Santaren JF, Alconada A (1993) Molecular chaperones and the biogenesis of mitochondria and peroxisomes. Biol Cell 77: 47–62PubMedCrossRefGoogle Scholar
  12. De Vries DD, Ruitenbeek W, de Wijs IJ, Trijbels JMF, van Oost BA (1993) Enzymological versus DNA investigations in mitochondrial (encephalo-myopathies). J Inherited Metab Dis 16: 534–536PubMedCrossRefGoogle Scholar
  13. Deshaies RJ, Koch BD, Werner-Washburne M, Craig EA, Schekman R (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332: 800–805PubMedCrossRefGoogle Scholar
  14. DeVivo DC (1993) The expanding clinical spectrum of mitochondrial diseases. Brain Dev 15: 1–22CrossRefGoogle Scholar
  15. DiMauro S, Moraes CT (1993) Mitochondrial encephalomyopathies. Arch Neurol 50: 1197–1208PubMedCrossRefGoogle Scholar
  16. DiMâuro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC (1985) Mitochondrial myopathies. Ann Neurol 17: 521–538PubMedCrossRefGoogle Scholar
  17. DiMauro S, Bonilla E, Zeviani M, Servidei S, DeVivo DC, Schon EA (1987) Mitochondrial myopathies. J Inherited Metab Dis 10 Suppl 11: 113–128CrossRefGoogle Scholar
  18. DiMauro S, Moraes CT, Shanske S, Lombes A, Nakase H, Mita S, Tritschler HJ, Bonilla E, Miranda AF, Schon EA (1991) Mitochondrial encephalomyopathies: biochemical approach. Rev Neurol 147: 443–449PubMedGoogle Scholar
  19. DiMauro S, Simonetti S, Chen X, Petruzzella V, Hirano M, Shanske S, Moraes CT, Schon EA (1993) Mitochondrial dysfunction as a mechanism of CNS injury. In: Waxman SG (ed) Molecular and cellular approaches to the treatment of neurological disease. Raven, New York, pp 67–79Google Scholar
  20. Eymard B, Hauw JJ (1992) Mitochondrial encephalomyopathies. Curr Opin Neurol Neurosurg 5: 909–916PubMedGoogle Scholar
  21. Gerbitz KD, Obermaier-Kusser B, Zierz S, Pongratz D, Müller-Höcker J, Lestienne P (1990) Mitochondrial myopathies: divergences of genetic deletions, biochemical defects and the clinical syndromes. J Neurol 237: 5–10PubMedCrossRefGoogle Scholar
  22. Gething MJ, Sambrook J (1992) Protein folding in the cell. Nature 355: 33–45PubMedCrossRefGoogle Scholar
  23. Glick B, Schatz G (1991) Import of proteins into mitochondria. Annu Rev Genet 25: 21–44PubMedCrossRefGoogle Scholar
  24. Glick BS, Beasley EM, Schatz G (1992) Protein sorting in mitochondria. Trends Biochem Sci 17: 453–459PubMedCrossRefGoogle Scholar
  25. Gupta RS (1990) Mitochondria, molecular chaperone proteins and the in vivo assembly of microtubules. Trends Biochem Sci 15: 415–418PubMedCrossRefGoogle Scholar
  26. Guzman M, Geelen MJH (1993) Regulation of fatty acid oxidation in mammalian liver. Biochim Biophys Acta 1167: 227–241PubMedCrossRefGoogle Scholar
  27. Haelestrap AP (1989) The regulation of the matrix volume of mammalian mitochondria in vivo and in vitro and its role in the control of mitochondrial metabolism. Biochim Biophys Acta 973: 355–382CrossRefGoogle Scholar
  28. Haginoya K, Miyabayashi S, Iinuma K, Tada K (1993) Quantitative evaluation of electron transport system proteins in mitochondrial encephalomyopathy. Acta Neuropathol (Berl) 85: 370–377CrossRefGoogle Scholar
  29. Hale DE, Bennett MJ (1992) Fatty acid oxidation disorders:a new class of metabolic diseases. J Pediatr 121: 1–11PubMedCrossRefGoogle Scholar
  30. Harding AE, Hammans SR (1992) Deletions of the mitochondrial genome. J Inherited Metab Dis 15: 480–486PubMedCrossRefGoogle Scholar
  31. Hausegger KA, Millner MM, Ebner F, Flückiger F, Justich E (1991) Mitochondrial encephalomyopathy–two years follow-up by MRI. Pediatr Radiol 21: 231–233PubMedCrossRefGoogle Scholar
  32. Hawlitschek G, Schneider H, Schmidt B, Tropschug M, Hartl FU, Neupert W (1988) Mitochondrial protein import: identification of processing peptidase and of PEP, a processing enhancing protein. Cell 53: 795–806PubMedCrossRefGoogle Scholar
  33. Holt IJ, Harding AE, Petty RKH, Morgan-Hughes JA (1990) A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 46: 428–433PubMedGoogle Scholar
  34. Horwich A (1990) Protein import into mitochondria and peroxisomes. Curr Opin Cell Biol 2: 625–633PubMedCrossRefGoogle Scholar
  35. Ishitsu T, Miike T, Kitano A, Haraguchi Y, Ohtani Y, Matsuda I, Shimoji A, Kimura H (1987) Heterogeneous phenotypes of mitochondrial encephalomyopathy in a single kindred. Neurology 37: 1867–1869PubMedCrossRefGoogle Scholar
  36. Kiebler M, Pfaller R, Söllner T, Griffiths G, Horstmann H, Pfanner N, Neupert W (1990) Identification of a mitochondrial receptor complex required for recognition and membrane insertion of precursor proteins. Nature 348: 610–616PubMedCrossRefGoogle Scholar
  37. Kroon AM, van den Bogert C (1987) Biogenesis of mitochondria and genetics of mitochondrial defects. J Inherited Metab Dis 10 Suppl 11: 54–61CrossRefGoogle Scholar
  38. Lightowlers RN (1992) Hereditary disorders including mito-chondrial diseases. Curr Opin Neurol Neurosurg 5: 368–374PubMedGoogle Scholar
  39. Lombes A, Bonilla E, Dimauro S (1989) Mitochondrial en-cephalomyopathies. Rev Neurol 145: 671–689PubMedGoogle Scholar
  40. Mannella CA (1992) The „ins“ and „outs” of mitochondrial membrane channels. Trends Biochem Sci 17: 315–320PubMedCrossRefGoogle Scholar
  41. Meijer AJ, van Noorden CIF (1991) Celbiologie in medisch perspectief. VI. Energievoorziening van de cel. Ned Tijdschr Geneeskd 135: 2164–2170PubMedGoogle Scholar
  42. Menkes JH (1987) Genetic disorders of mitochondrial function. J Pediatr 110: 255–259PubMedCrossRefGoogle Scholar
  43. Morgan-Hughes JA (1982) Mitochondrial myopathies. In: Mastaglia FL, Walton J (eds) Skeletal muscle pathology. Churchill Livingstone, Edinburgh, pp 309–339Google Scholar
  44. Munnich A, Rustin P, Rötig A, Chretien D, Bonnefont JP, Nut-tin C, Cormier V, Vassault A, Parvy P, Bardet J, Charpentier C, Rabier D, Saudubray JM (1992) Clinical aspects of mitochondrial disorders. J Inherited Metab Dis 15: 448–455PubMedCrossRefGoogle Scholar
  45. Ozawa T, Tanaka M, Suzuki H, Nishikimi M (1987) Structure and function of mitochondria: their organization and disorders. Brain Dev 9: 76–81PubMedCrossRefGoogle Scholar
  46. Pfanner N, Neupert W (1990) The mitochondrial protein import apparatus. Annu Rev Biochem 59: 331–353PubMedCrossRefGoogle Scholar
  47. Poulton J (1992) Duplications of mitochondrial DNA: implica-tions for pathogenesis. J Inherited Metab Dis 15: 487–498PubMedCrossRefGoogle Scholar
  48. Poulton J (1993) Mitochondrial DNA and genetic disease. Dev Med Child Neurol 35: 833–840PubMedCrossRefGoogle Scholar
  49. Przyrembel (1987) Therapy of mitochondrial disorders. J Inherited Metab Dis 10: 129–146PubMedCrossRefGoogle Scholar
  50. Ruitenbeek W, Sengers RCA, Trijbels JMF, Janssen AJM, Bakkeren JAJM (1992) The use of chorionic villi in prenatal diagnosis of mitochondriopathies. J Inherited Metab Dis 15: 303–306PubMedCrossRefGoogle Scholar
  51. Scholte HR, Busch HFM, Luyt-Houwen IEM, Vaandrager-Verduin MHM, Przyrembel H, Arts WFM (1987) Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells. J Inherited Metab Dis 10 Suppl 11: 81–97CrossRefGoogle Scholar
  52. Schulz H (1991) Beta oxidation of fatty acids. Biochim Biophys Acta 1081: 109–120PubMedCrossRefGoogle Scholar
  53. Sengers RCA, Stadhouders AM (1987) Secondary mitochondrial pathology. J Inherited Metab Dis 10 Supp 11: 98–104CrossRefGoogle Scholar
  54. Sengers RCA, Stadhouders AM, Trijbels JMF (1984) Mitochondrial myopathies. Eur J Pediatr 141: 192–207PubMedCrossRefGoogle Scholar
  55. Shoffner JM, Wallace DC (1992) Mitochondrial genetics: principles and practice. Am J Hum Genet 51: 1179–1186PubMedGoogle Scholar
  56. Siciliano G, Rossi B Angelini C, Martinuzzi A, Carrozzo R, Bevilacqua G, Viacava P, Federico A, Fabrizi GM, Muratorio A (1992) Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy. Neuro-musc Dis 2: 397–404CrossRefGoogle Scholar
  57. Stadhouders AM, Sengers RCA (1987) Morphological observations in skeletal muscle from patients with a mitochondrial myopathy. J Inherited Metab Dis 10 Supp 11: 6280Google Scholar
  58. Tager JM, Aarts JMFG, Van den Bogert C, Wanders RJA (1994) Signals on proteins, intracellular targeting and inborn errors of metabolism. J Inherited Metab Dis 17: 459–469PubMedCrossRefGoogle Scholar
  59. Tritschler HJ, Medori R (1993) Mitochondrial DNA alterations as a source of human disorders. Neurology 43: 280–288PubMedCrossRefGoogle Scholar
  60. Tulinius MH, Holme E, Kristiansson B, Larsson NG, Oldfors A (1991) Mitochondrial encephalomyopathies in childhood.Google Scholar
  61. Tulinius MH, Holme E, Kristiansson B, Larsson NG, Oldfors A (1991) Mitochondrial encephalomyopathies in childhood.Google Scholar
  62. II. Clinical manifestations and syndromes. J Pediatr 119: 251–259Google Scholar
  63. Vianey-Liaud C, Divry P, Gregersen N, Mathieu M (1987) The inborn errors of mitochondrial fatty acid oxidation. J Inherited Metab Dis 10 Suppl 1j: 159–198CrossRefGoogle Scholar
  64. Wallace DC (1992) Mitochondrial genetics:a paradigm for aging and degenerative diseases? Science 256: 628–632PubMedCrossRefGoogle Scholar
  65. Wallace DC, Lott MT, Shoffner JM, Brown MD (1992) Diseases resulting from mitochondrial DNA point mutations. J Inherited Metab Dis 15: 472–479PubMedCrossRefGoogle Scholar
  66. Wienhues U, Becker K, Schleyer M, Guiard B, Tropschug M, Horwich AL, Pfanner N, Neupert W (1991) Protein folding causes an arrest of preprotein translocation into mitochondria in vivo. J Cell Biol 115: 1601–1609PubMedCrossRefGoogle Scholar
  67. Zeviani M, Bonilla E, DeVivo DC, DiMauro S (1989) Mitochondrial diseases. Neurol Clin 7: 123–156PubMedGoogle Scholar
  68. Zeviani M, DiDonato S (1991) Neurological disorders due to mutations of the mitochondrial genome. Neuromusc Dis 1: 165–172PubMedCrossRefGoogle Scholar
  69. Zeviani M (1992) Nucleus-driven mutations of human mitochondrial DNA. J Inherited Metab Dis 15: 456–471PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Marjo S. van der Knaap
    • 1
  • Jacob Valk
    • 2
  1. 1.Department of Child NeurologyFree University HospitalAmsterdamThe Netherlands
  2. 2.Department of Diagnostic RadiologyFree University HospitalAmsterdamThe Netherlands

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