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Mitochondrial Dysfunction in Neurodegenerative Disorders pp 3–30Cite as

An Introduction to Mitochondria, Their Structure and Functions

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Abstract

Mitochondria are essential intracellular organelles whose central role in maintaining energy homeostasis places them at the heart of cell integrity, function and survival. As the reliable provision of energy is so fundamental to every aspect of cellular function, mitochondrial dysfunction inevitably has devastating implications for the cell, the tissue and the organism. This is especially critical in the nervous system, where subtle changes in signalling and function can have catastrophic global consequences. Further, as postmitotic cells are heavily dependent on oxidative phosphorylation and are morphologically enormously complex, neurons pose a unique set of challenges for the mitochondrial population that reside within them. Mitochondrial dysfunction has profound consequences for the nervous system and is implicated in a host of neurological and neurodegenerative diseases. The following chapter introduces the form and function of these fascinating organelles and introduces key concepts and vulnerabilities that may underlie their involvement in neurodegenerative conditions. This introduction lays the foundation for the following chapters, which will explore specific aspects of the roles of these organelles in a range of neurodegenerative disease.

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References

  1. Margulis L, editor. Origin of eukaryotic cells. New Haven: Yale University Press; 1970.

    Google Scholar 

  2. Martin W, Mentel M. The origin of mitochondria. Natl Educ. 2010;3(9):58.

    Google Scholar 

  3. Embley TM, Martin W. Eukaryotic evolution, changes and challenges. Nature. 2006;440(7084):623–30.

    Article  CAS  PubMed  Google Scholar 

  4. Gray MW. The endosymbiont hypothesis revisited. Int Rev Cytol. 1992;141:233–357.

    Article  CAS  PubMed  Google Scholar 

  5. Altman R. Die Elementarorganismen Und Ihre Beziehungen Zu Den Zellen. Leipzing: Zeit & Comp; 1890. p. 145.

    Google Scholar 

  6. Battelli F, Stern L. Die Oxydationsfermente. Ergebn Physiol Biol Chem Exp Pharmakol. 1912;15:96–268.

    Article  Google Scholar 

  7. Benda C. Ueber die Spermatogenese der Vertebraten und höherer Evertebraten, II. Theil: Die Histiogenese der Spermien. Arch Anat Physiol. 1898;73:393–8.

    Google Scholar 

  8. Palade GE. The fine structure of mitochondria. Anat Rec. 1952;114(3):427–51.

    Article  CAS  PubMed  Google Scholar 

  9. Neupert W, Herrmann JM. Translocation of proteins into mitochondria. Ann Rev Biochem. 2007;76:723–49.

    Article  CAS  PubMed  Google Scholar 

  10. Chacinska A, Pfannschmidt S, Wiedemann N, Kozjak V, Sanjuan Szklarz LK, Schulze-Specking A, et al. Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J. 2004;23(19):3735–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Naoe M, Ohwa Y, Ishikawa D, Ohshima C, Nishikawa S, Yamamoto H, et al. Identification of Tim40 that mediates protein sorting to the mitochondrial intermembrane space. J Biol Chem. 2004;279(46):47815–21.

    Article  CAS  PubMed  Google Scholar 

  12. Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci. 2000;25(7):319–24.

    Article  CAS  PubMed  Google Scholar 

  13. Mannella CA. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim Biophys Acta. 2006;1763(5–6):542–8.

    Article  CAS  PubMed  Google Scholar 

  14. Vogel F, Bornhovd C, Neupert W, Reichert AS. Dynamic subcompartmentalization of the mitochondrial inner membrane. J Cell Biol. 2006;175(2):237–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cogliati S, Frezza C, Soriano ME, Varanita T, Quintana-Cabrera R, Corrado M, et al. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell. 2013;155(1):160–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Acin-Perez R, Enriquez JA. The function of the respiratory supercomplexes: the plasticity model. Biochim Biophys Acta. 2014;1837(4):444–50.

    Article  CAS  PubMed  Google Scholar 

  17. Genova ML, Lenaz G. Functional role of mitochondrial respiratory supercomplexes. Biochim Biophys Acta. 2014;1837(4):427–43.

    Article  CAS  PubMed  Google Scholar 

  18. Koopman WJ, Nijtmans LG, Dieteren CE, Roestenberg P, Valsecchi F, Smeitink JA, et al. Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation. Antioxid Redox Signal. 2010;12(12):1431–70.

    Article  CAS  PubMed  Google Scholar 

  19. Efremov RG, Baradaran R, Sazanov LA. The architecture of respiratory complex I. Nature. 2010;465(7297):441–5.

    Article  CAS  PubMed  Google Scholar 

  20. Cecchini G. Function and structure of complex II of the respiratory chain. Ann Rev Biochem. 2003;72:77–109.

    Article  CAS  PubMed  Google Scholar 

  21. Iwata S, Lee JW, Okada K, Lee JK, Iwata M, Rasmussen B, et al. Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science (New York, NY). 1998;281(5373):64–71.

    Article  CAS  Google Scholar 

  22. Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, et al. The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A. Science (New York, NY). 1996;272(5265):1136–44.

    Article  CAS  Google Scholar 

  23. Ferguson SJ. ATP synthase: what dictates the size of a ring? Curr Biol. 2000;10(21):R804–8.

    Article  CAS  PubMed  Google Scholar 

  24. Yoshida M, Muneyuki E, Hisabori T. ATP synthase – a marvellous rotary engine of the cell. Nat Rev Mol Cell Biol. 2001;2(9):669–77.

    Article  CAS  PubMed  Google Scholar 

  25. Liu Y and Levine B. Autosis and autophagic cell death: the dark side of autophagy. Cell Death and Differentiation. 2015;22:367–73.

    Google Scholar 

  26. Pradelli LA, Beneteau M, Ricci JE. Mitochondrial control of caspase-dependent and -independent cell death. Cell Mol Life Sci. 2010;67(10):1589–97.

    Article  CAS  PubMed  Google Scholar 

  27. Orrenius S, Gogvadze V, Zhivotovsky B. Calcium and mitochondria in the regulation of cell death. Biochem Biophys Res Commun. 2015;460(1):72–81.

    Article  CAS  PubMed  Google Scholar 

  28. Morciano G, Giorgi C, Bonora M, Punzetti S, Pavasini R, Wieckowski MR, et al. Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury. J Mol Cell Cardiol. 2015;78:142–53.

    Article  CAS  PubMed  Google Scholar 

  29. Morciano G, Giorgi C, Balestra D, Marchi S, Perrone D, Pinotti M, et al. Mcl-1 involvement in mitochondrial dynamics is associated with apoptotic cell death. Mol Biol Cell. 2016;1:20–34.

    Google Scholar 

  30. Bonora M, Pinton P. The mitochondrial permeability transition pore and cancer: molecular mechanisms involved in cell death. Front Oncol. 2014;4:302.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fatokun AA, Dawson VL, Dawson TM. Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol. 2014;171(8):2000–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Virag L, Robaszkiewicz A, Rodriguez-Vargas JM, Oliver FJ. Poly(ADP-ribose) signaling in cell death. Mol Aspects Med. 2013;34(6):1153–67.

    Article  CAS  PubMed  Google Scholar 

  33. Andrabi SA, Dawson TM, Dawson VL. Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann N Y Acad Sci. 2008;1147:233–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Patron M, Raffaello A, Granatiero V, Tosatto A, Merli G, De Stefani D, et al. The mitochondrial calcium uniporter (MCU): molecular identity and physiological roles. J Biol Chem. 2013;288(15):10750–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kamer KJ, Mootha VK. MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter. EMBO Rep. 2014;15(3):299–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sancak Y, Markhard AL, Kitami T, Kovacs-Bogdan E, Kamer KJ, Udeshi ND, et al. EMRE is an essential component of the mitochondrial calcium uniporter complex. Science (New York, NY). 2013;342(6164):1379–82.

    Article  CAS  Google Scholar 

  37. Kamer KJ, Mootha VK. The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol. 2015;16(9):545–53.

    Article  CAS  PubMed  Google Scholar 

  38. Boyman L, Williams GS, Khananshvili D, Sekler I, Lederer WJ. NCLX: the mitochondrial sodium calcium exchanger. J Mol Cell Cardiol. 2013;59:205–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Palty R, Hershfinkel M, Sekler I. Molecular identity and functional properties of the mitochondrial Na+/Ca2+ exchanger. J Biol Chem. 2012;287(38):31650–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Palty R, Sekler I. The mitochondrial Na(+)/Ca(2+) exchanger. Cell Calcium. 2012;52(1):9–15.

    Article  CAS  PubMed  Google Scholar 

  41. Gincel D, Zaid H, Shoshan-Barmatz V. Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function. Biochem J. 2001;358(Pt 1):147–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Keinan N, Pahima H, Ben-Hail D, Shoshan-Barmatz V. The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis. Biochim Biophys Acta. 2013;1833(7):1745–54.

    Article  CAS  PubMed  Google Scholar 

  43. Weisthal S, Keinan N, Ben-Hail D, Arif T, Shoshan-Barmatz V. Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction. Biochim Biophys Acta. 2014;1843(10):2270–81.

    Article  CAS  PubMed  Google Scholar 

  44. Clapham DE. Calcium signaling. Cell. 2007;131(6):1047–58.

    Article  CAS  PubMed  Google Scholar 

  45. Boitier E, Rea R, Duchen MR. Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes. J Cell Biol. 1999;145(4):795–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tinel H, Cancela JM, Mogami H, Gerasimenko JV, Gerasimenko OV, Tepikin AV, et al. Active mitochondria surrounding the pancreatic acinar granule region prevent spreading of inositol trisphosphate-evoked local cytosolic Ca(2+) signals. EMBO J. 1999;18(18):4999–5008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Babcock DF, Hille B. Mitochondrial oversight of cellular Ca2+ signaling. Curr Opin Neurobiol. 1998;8(3):398–404.

    Article  CAS  PubMed  Google Scholar 

  48. Jouaville LS, Pinton P, Bastianutto C, Rutter GA, Rizzuto R. Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc Natl Acad Sci U S A. 1999;96(24):13807–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. McCormack JG, Halestrap AP, Denton RM. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev. 1990;70(2):391–425.

    CAS  PubMed  Google Scholar 

  50. Bruton JD, Aydin J, Yamada T, Shabalina IG, Ivarsson N, Zhang SJ, et al. Increased fatigue resistance linked to Ca2+-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice. J Physiol. 2010;588(Pt 21):4275–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lill R. Function and biogenesis of iron-sulphur proteins. Nature. 2009;460(7257):831–8.

    Article  CAS  PubMed  Google Scholar 

  52. Adam AC, Bornhovd C, Prokisch H, Neupert W, Hell K. The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria. EMBO J. 2006;25(1):174–83.

    Article  CAS  PubMed  Google Scholar 

  53. Lange H, Kaut A, Kispal G, Lill R. A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins. Proc Natl Acad Sci U S A. 2000;97(3):1050–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Paradkar PN, Zumbrennen KB, Paw BH, Ward DM, Kaplan J. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol Cell Biol. 2009;29(4):1007–16.

    Article  CAS  PubMed  Google Scholar 

  55. Tong WH, Rouault T. Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J. 2000;19(21):5692–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tong W-H, Jameson GNL, Huynh BH, Rouault TA. Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster. Proc Natl Acad Sci U S A. 2003;100(17):9762–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  58. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell. 2006;127(2):397–408.

    Article  CAS  PubMed  Google Scholar 

  59. Giorgio M, Trinei M, Migliaccio E, Pelicci PG. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol. 2007;8(9):722–8.

    Article  CAS  PubMed  Google Scholar 

  60. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24(5):981–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Connerth M, Tatsuta T, Haag M, Klecker T, Westermann B, Langer T. Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein. Science (New York, NY). 2012;338(6108):815–8.

    Article  CAS  Google Scholar 

  62. Tatsuta T, Scharwey M, Langer T. Mitochondrial lipid trafficking. Trends Cell Biol. 2014;24(1):44–52.

    Article  CAS  PubMed  Google Scholar 

  63. Gohil VM, Greenberg ML. Mitochondrial membrane biogenesis: phospholipids and proteins go hand in hand. J Cell Biol. 2009;184(4):469–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell. 2010;141(4):656–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Bonello S, Zahringer C, BelAiba RS, Djordjevic T, Hess J, Michiels C, et al. Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arterioscler Thromb Vasc Biol. 2007;27(4):755–61.

    Article  CAS  PubMed  Google Scholar 

  66. Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem. 2000;275(33):25130–8.

    Article  CAS  PubMed  Google Scholar 

  67. Galanis A, Pappa A, Giannakakis A, Lanitis E, Dangaj D, Sandaltzopoulos R. Reactive oxygen species and HIF-1 signalling in cancer. Cancer Lett. 2008;266(1):12–20.

    Article  CAS  PubMed  Google Scholar 

  68. Hamanaka RB, Chandel NS. Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci. 2010;35(9):505–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. D’Autreaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol. 2007;8(10):813–24.

    Article  PubMed  CAS  Google Scholar 

  70. Albring M, Griffith J, Attardi G. Association of a protein structure of probable membrane derivation with HeLa cell mitochondrial DNA near its origin of replication. Proc Natl Acad Sci U S A. 1977;74(4):1348–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Holt IJ, He J, Mao C-C, Boyd-Kirkup JD, Martinsson P, Sembongi H, et al. Mammalian mitochondrial nucleoids: organizing an independently minded genome. Mitochondrion. 2007;7(5):311–21.

    Article  CAS  PubMed  Google Scholar 

  72. Kukat C, Wurm CA, Spahr H, Falkenberg M, Larsson NG, Jakobs S. Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proc Natl Acad Sci U S A. 2011;108(33):13534–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kukat C, Davies KM, Wurm CA, Spahr H, Bonekamp NA, Kuhl I, et al. Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc Natl Acad Sci U S A. 2015;112(36):11288–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290(5806):457–65.

    Article  CAS  PubMed  Google Scholar 

  75. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 1999;23(2):147.

    Article  CAS  PubMed  Google Scholar 

  76. Claros MG, Perea J, Shu Y, Samatey FA, Popot JL, Jacq C. Limitations to in vivo import of hydrophobic proteins into yeast mitochondria. The case of a cytoplasmically synthesized apocytochrome b. Eur J Biochem/FEBS. 1995;228(3):762–71.

    Article  CAS  Google Scholar 

  77. Wallace DC. Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine. Annu Rev Biochem. 2007;76:781–821.

    Article  CAS  PubMed  Google Scholar 

  78. Clayton DA. Replication of animal mitochondrial DNA. Cell. 1982;28(4):693–705.

    Article  CAS  PubMed  Google Scholar 

  79. Clayton DA. Mitochondrial DNA, replication: what we know. IUBMB Life. 2003;55(4–5):213–7.

    Article  CAS  PubMed  Google Scholar 

  80. Schwartz M, Vissing J. Paternal inheritance of mitochondrial DNA. N Engl J Med. 2002;347(8):576–80.

    Article  PubMed  Google Scholar 

  81. Clayton DA. Replication and transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol. 1991;7:453–78.

    Article  CAS  PubMed  Google Scholar 

  82. Brewer BJ, Fangman WL. A replication fork barrier at the 3′ end of yeast ribosomal RNA genes. Cell. 1988;55(4):637–43.

    Article  CAS  PubMed  Google Scholar 

  83. Holt IJ, Lorimer HE, Jacobs HT. Coupled leading- and lagging-strand synthesis of mammalian mitochondrial DNA. Cell. 2000;100(5):515–24.

    Article  CAS  PubMed  Google Scholar 

  84. Grossman LI, Watson R, Vinograd J. The presence of ribonucleotides in mature closed-circular mitochondrial DNA. Proc Natl Acad Sci U S A. 1973;70(12):3339–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yasukawa T, Reyes A, Cluett TJ, Yang MY, Bowmaker M, Jacobs HT, et al. Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand. EMBO J. 2006;25(22):5358–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Reyes A, Kazak L, Wood SR, Yasukawa T, Jacobs HT, Holt IJ. Mitochondrial DNA replication proceeds via a ‘bootlace’ mechanism involving the incorporation of processed transcripts. Nucleic Acids Res. 2013;41(11):5837–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Korhonen JA, Pham XH, Pellegrini M, Falkenberg M. Reconstitution of a minimal mtDNA replisome in vitro. EMBO J. 2004;23(12):2423–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Fuste JM, Wanrooij S, Jemt E, Granycome CE, Cluett TJ, Shi Y, et al. Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication. Mol Cell. 2010;37(1):67–78.

    Article  CAS  PubMed  Google Scholar 

  89. Tuppen HA, Blakely EL, Turnbull DM, Taylor RW. Mitochondrial DNA mutations and human disease. Biochim Biophys Acta. 2010;1797(2):113–28.

    Article  CAS  PubMed  Google Scholar 

  90. Copeland WC. Inherited mitochondrial diseases of DNA replication. Annu Rev Med. 2008;59:131–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gredilla R, Bohr VA, Stevnsner T. Mitochondrial DNA repair and association with aging – an update. Exp Gerontol. 2010;45(7–8):478–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bohr VA. Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells. Free Radic Biol Med. 2002;32(9):804–12.

    Article  CAS  PubMed  Google Scholar 

  93. Satoh MS, Huh NH, Rajewsky MF, Kuroki T. Enzymatic removal of O-6-ethylguanine from mitochondrial-DNA in rat-tissues exposed to N-ethyl-N-nitrosourea in vivo. J Biol Chem. 1988;263(14):6854–6.

    CAS  PubMed  Google Scholar 

  94. Boesch P, Weber-Lotfi F, Ibrahim N, Tarasenko V, Cosset A, Paulus F, et al. DNA repair in organelles: pathways, organization, regulation, relevance in disease and aging. Biochim Biophys Acta. 2011;1813(1):186–200.

    Article  CAS  PubMed  Google Scholar 

  95. Muller-Hocker J, Seibel P, Schneiderbanger K, Kadenbach B. Different in situ hybridization patterns of mitochondrial DNA in cytochrome c oxidase-deficient extraocular muscle fibres in the elderly. Virchows Arch A Pathol Anat Histopathol. 1993;422(1):7–15.

    Article  CAS  PubMed  Google Scholar 

  96. Schwarze SR, Lee CM, Chung SS, Roecker EB, Weindruch R, Aiken JM. High-levels of mitochondrial-DNA deletions in skeletal-muscle of old rhesus-monkeys. Mech Ageing Dev. 1995;83(2):91–101.

    Article  CAS  PubMed  Google Scholar 

  97. Liu VW, Zhang C, Nagley P. Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing. Nucleic Acid Res. 1998;26(5):1268–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Elson JL, Samuels DC, Turnbull DM, Chinnery PF. Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age. Am J Hum Genet. 2001;68:802–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Lightowlers RN, Chinnery PF, Turnbull DM, Howell N. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet. 1997;13(11):450–5.

    Article  CAS  PubMed  Google Scholar 

  100. He YP, Wu J, Dressman DC, Iacobuzio-Donahue C, Markowitz SD, Velculescu VE, et al. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010;464(7288):610–U175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sacconi S, Salviati L, Nishigaki Y, Walker WF, Hernandez-Rosa E, Trevisson E, et al. A functionally dominant mitochondrial DNA mutation. Hum Mol Genet. 2008;17(12):1814–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Falkenberg M, Larsson NG, Gustafsson CM. DNA replication and transcription in mammalian mitochondria. Ann Rev Biochem. 2007;76:679–99.

    Article  CAS  PubMed  Google Scholar 

  103. Holzmann J, Frank P, Loffler E, Bennett KL, Gerner C, Rossmanith W. RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell. 2008;135(3):462–74.

    Article  CAS  PubMed  Google Scholar 

  104. Temperley RJ, Wydro M, Lightowlers RN, Chrzanowska-Lightowlers ZM. Human mitochondrial mRNAs – like members of all families, similar but different. Biochim Biophys Acta. 2010;1797(6–7):1081–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Nagaike T, Suzuki T, Tomari Y, Takemoto-Hori C, Negayama F, Watanabe K, et al. Identification and characterization of mammalian mitochondrial tRNA nucleotidyltransferases. J Biol Chem. 2001;276(43):40041–9.

    Article  CAS  PubMed  Google Scholar 

  106. Tomecki R, Dmochowska A, Gewartowski K, Dziembowski A, Stepien PP. Identification of a novel human nuclear-encoded mitochondrial poly(A) polymerase. Nucleic Acids Res. 2004;32(20):6001–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Crosby AH, Patel H, Chioza BA, Proukakis C, Gurtz K, Patton MA, et al. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am J Hum Genet. 2010;87(5):655–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Slomovic S, Schuster G. Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA. RNA. 2008;14(2):310–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Koc E, Haque MD, Spremulli LL. Current views of the structure of the mammalian mitochondrial ribosome. Isr J Chem. 2010;50(1):45–59.

    Article  CAS  Google Scholar 

  110. Chrzanowska-Lightowlers ZM, Horvath R, Lightowlers RN. 175th ENMC international workshop: mitochondrial protein synthesis in health and disease, 25–27th June 2010, Naarden, The Netherlands. Neuromuscul Disord. 2011;21(2):142–7.

    Article  CAS  PubMed  Google Scholar 

  111. Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell. 2005;123(2):277–89.

    Article  CAS  PubMed  Google Scholar 

  112. Di Bella D, Lazzaro F, Brusco A, Plumari M, Battaglia G, Pastore A, et al. Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet. 2010;42(4):313–21.

    Article  PubMed  CAS  Google Scholar 

  113. Das G, Varshney U. Peptidyl-tRNA hydrolase and its critical role in protein biosynthesis. Microbiology. 2006;152(Pt 8):2191–5.

    Article  CAS  PubMed  Google Scholar 

  114. Keiler KC, Waller PR, Sauer RT. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science (New York, NY). 1996;271(5251):990–3.

    Article  CAS  Google Scholar 

  115. Muto A, Ushida C, Himeno H. A bacterial RNA that functions as both a tRNA and an mRNA. Trends Biochem Sci. 1998;23(1):25–9.

    Article  CAS  PubMed  Google Scholar 

  116. Temperley R, Richter R, Dennerlein S, Lightowlers RN, Chrzanowska-Lightowlers ZM. Hungry codons promote frameshifting in human mitochondrial ribosomes. Science (New York, NY). 2010;327(5963):301.

    Article  CAS  Google Scholar 

  117. Soleimanpour-Lichaei HR, Kuhl I, Gaisne M, Passos JF, Wydro M, Rorbach J, et al. mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Mol Cell. 2007;27(5):745–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Richter R, Rorbach J, Pajak A, Smith PM, Wessels HJ, Huynen MA, et al. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J. 2010;29(6):1116–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Antonicka H, Ostergaard E, Sasarman F, Weraarpachai W, Wibrand F, Pedersen AM, et al. Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect. Am J Hum Genet. 2010;87(1):115–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Handa Y, Inaho N, Nameki N. YaeJ is a novel ribosome-associated protein in Escherichia coli that can hydrolyze peptidyl-tRNA on stalled ribosomes. Nucleic Acids Res. 2011;39(5):1739–48.

    Article  CAS  PubMed  Google Scholar 

  121. Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science (New York, NY). 2012;337(6098):1062–5.

    Article  CAS  Google Scholar 

  122. Chan DC. Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol. 2006;22:79–99.

    Article  CAS  PubMed  Google Scholar 

  123. Rojo JV, Merino AM, Gonzalez LO, Vizoso F. Expression and clinical significance of pepsinogen C in epithelial ovarian carcinomas. Eur J Obstet Gynaecol Reprod Biol. 2002;104(1):58–63.

    Article  CAS  Google Scholar 

  124. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160(2):189–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM. Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J Biol Chem. 2004;279(18):18792–8.

    Article  CAS  PubMed  Google Scholar 

  126. Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet. 2000;26(2):207–10.

    Article  CAS  PubMed  Google Scholar 

  127. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol. 2010;11(12):872–84.

    Article  CAS  PubMed  Google Scholar 

  128. Schmid SL, Frolov VA. Dynamin: functional design of a membrane fission catalyst. Annu Rev Cell Dev Biol. 2011;27:79–105.

    Article  CAS  PubMed  Google Scholar 

  129. Smirnova E, Griparic L, Shurland DL, van der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell. 2001;12(8):2245–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Dohm JA, Lee SJ, Hardwick JM, Hill RB, Gittis AG. Cytosolic domain of the human mitochondrial fission protein Fis1 adopts a TPR fold. Proteins. 2004;54(1):153–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Lee YJ, Jeong SY, Karbowski M, Smith CL, Youle RJ. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol Biol Cell. 2004;15(11):5001–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, et al. The Parkinson’s disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci. 2013;16(9):1257–U135.

    Article  CAS  PubMed  Google Scholar 

  133. Osellame LD, Rahim AA, Hargreaves IP, Gegg ME, Richard-Londt A, Brandner S, et al. Mitochondria and quality control defects in a mouse model of Gaucher disease – links to Parkinson’s disease. Cell Metab. 2013;17(6):941–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Osellame LD, Duchen MR. Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration. Br J Pharmacol. 2014;171(8):1958–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Chen S, Owens GC, Crossin KL, Edelman DB. Serotonin stimulates mitochondrial transport in hippocampal neurons. Mol Cell Neurosci. 2007;36(4):472–83.

    Article  CAS  PubMed  Google Scholar 

  136. Overly CC, Rieff HI, Hollenbeck PJ. Organelle motility and metabolism in axons vs dendrites of cultured hippocampal neurons. J Cell Sci. 1996;109(Pt 5):971–80.

    CAS  PubMed  Google Scholar 

  137. Waters J, Smith SJ. Mitochondria and release at hippocampal synapses. Pflugers Arch. 2003;447(3):363–70.

    Article  CAS  PubMed  Google Scholar 

  138. Saxton WM, Hollenbeck PJ. The axonal transport of mitochondria. J Cell Sci. 2012;125(Pt 9):2095–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Baas PW, Black MM, Banker GA. Changes in microtubule polarity orientation during the development of hippocampal neurons in culture. J Cell Biol. 1989;109(6 Pt 1):3085–94.

    Article  CAS  PubMed  Google Scholar 

  140. Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem. 2008;283(14):9089–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Reeve AK, Ludtmann MH, Angelova PR, Simcox EM, Horrocks MH, Klenerman D, et al. Aggregated alpha-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons. Cell Death Dis. 2015;6:e1820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Newcastle University Medical School, Wellcome Trust Centre for Mitochondrial Research, Newcastle upon Tyne, UK

    Eve Michelle Simcox BSc(hons), PhD & Amy Katherine Reeve BSc(hons), PhD

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  1. Eve Michelle Simcox BSc(hons), PhD
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  2. Amy Katherine Reeve BSc(hons), PhD
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Correspondence to Amy Katherine Reeve BSc(hons), PhD .

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Editors and Affiliations

  1. Newcastle University Medical School, Well. Trust Ctr. for Mitochondrial Res., Newcastle upon Tyne, United Kingdom

    Amy K. Reeve

  2. Newcastle University Medical School, Well. Trust Ctr. for Mitochondrial Res., Newcastle upon Tyne, United Kingdom

    Eve M. Simcox

  3. Cell and Developmental Biology, University College London, London, United Kingdom

    Michael R. Duchen

  4. Newcastle University Medical School, Well. Trust Ctr. for Mitochondrial Res., Newcastle upon Tyne, United Kingdom

    Doug M. Turnbull

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Simcox, E.M., Reeve, A.K. (2016). An Introduction to Mitochondria, Their Structure and Functions. In: Reeve, A., Simcox, E., Duchen, M., Turnbull, D. (eds) Mitochondrial Dysfunction in Neurodegenerative Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-28637-2_1

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