Export file:

Format

  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text

Content

  • Citation Only
  • Citation and Abstract

The ubiquitous role of mitochondria in Parkinson and other neurodegenerative diseases

Department of Informatics, Ionian University, Plateia Tsirigoti 7, 49100, Corfu, Greece

Special Issues: Novel modeling methodologies for the neuropathological dimensions of Parkinson’s disease

Orderly mitochondrial life cycle, plays a key role in the pathology of neurodegenerative diseases. Mitochondria are ubiquitous in neurons as they respond to an ever-changing demand for energy supply. Mitochondria constantly change in shape and location, feature of their dynamic nature, which facilitates a quality control mechanism. Biological studies in mitochondria dynamics are unveiling the mechanisms of fission and fusion, which essentially arrange morphology and motility of these organelles. Control of mitochondrial network homeostasis is a critical factor for the proper function of neurons. Disease-related genes have been reported to be implicated in mitochondrial dysfunction. Increasing evidence implicate mitochondrial perturbation in neuronal diseases, such as AD, PD, HD, and ALS. The intricacy involved in neurodegenerative diseases and the dynamic nature of mitochondria point to the idea that, despite progress toward detecting the biology underlying mitochondrial disorders, its link to these diseases is difficult to be identified in the laboratory. Considering the need to model signaling pathways, both in spatial and temporal level, there is a challenge to use a multiscale modeling framework, which is essential for understanding the dynamics of a complex biological system. The use of computational models in order to represent both a qualitative and a quantitative structure of mitochondrial homeostasis, allows to perform simulation experiments so as to monitor the conformational changes, as well as the intersection of form and function.
  Figure/Table
  Supplementary
  Article Metrics

Keywords Parkinson’ disease; Alzheimer’s disease; neurodegeneration; mitochondria dynamics; protein aggregation; fusion; fission

Citation: Georgia Theocharopoulou. The ubiquitous role of mitochondria in Parkinson and other neurodegenerative diseases. AIMS Neuroscience, 2020, 7(1): 43-65. doi: 10.3934/Neuroscience.2020004

References

  • 1. Gonatas N, Shy G (1965) Childhood myopathies with abnormal mitochondria. In Proceedings of the Vth International Congress of Neuropathology 100: 606–612.
  • 2. Baron M, Kudin AP, Kunz WS (2007) Mitochondrial dysfunction in neurodegenerative disorders. Biochem Soc Trans 35: 1228–1231.    
  • 3. DiMauro S (2011) A history of mitochondrial diseases. J Inherit Metab Dis 34: 261–276.    
  • 4. Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60: 748–766.    
  • 5. Federico A, Cardaioli E, Da Pozzo P, et al. (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322: 254–262.    
  • 6. De Vos KJ, Grierson AJ, Ackerley S, et al. (2008) Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 31: 151–173.    
  • 7. Chen H, Chan DC (2009) Mitochondrial dynamics–fusion, fission, movement, and mitophagy–in neurodegenerative diseases. Hum Mol Genet 18: R169–R176.    
  • 8. Wang X, Su B, Zheng L, et al. (2009) The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J Neurochem 109: 153–159.    
  • 9. Büeler H (2009) Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease. Exp Neurol 218: 235–246.    
  • 10. Park JS, Davis RL, Sue CM (2018) Mitochondrial dysfunction in Parkinson's disease: new mechanistic insights and therapeutic perspectives. Curr Neurol Neurosci Rep 18: 21.    
  • 11. Alexiou A, Vlamos P, Volikas K (2010) A Theoretical Artificial Approach on Reducing Mitochondrial Abnormalities in Alzheimer Disease. In Proceedings of the 10th IEEE International Conference on Information Technology and Applications in Biomedicin, IEEE: 1–4.
  • 12. Benard G, Karbowski M (2009) Mitochondrial fusion and division: regulation and role in cell viability. Semin Cell Dev Biol 20: 365–374.    
  • 13. Zorov DB, Vorobjev IA, Popkov VA, et al. (2019) Lessons from the Discovery of Mitochondrial Fragmentation (Fission): A Review and Update. Cells 8: 175.    
  • 14. Sheng ZH (2017) The interplay of axonal energy homeostasis and mitochondrial trafficking and anchoring. Trends Cell Biol 27: 403–416.    
  • 15. Lin MY, Sheng ZH (2015) Regulation of mitochondrial transport in neurons. Expe Cell Res 334: 35–44.    
  • 16. Mishra P, Chan DC (2016) Metabolic regulation of mitochondrial dynamics. J Cell Biol 212: 379–387.    
  • 17. Dickey AS, Strack S (2011) PKA/AKAP1 and PP2A/Bβ>2 regulate neuronal morphogenesis via Drp1 phosphorylation and mitochondrial bioenergetics. J Neurosci 31: 15716–15726.    
  • 18. Kuznetsov AV, Hermann M, Saks V, et al. (2009) The cell-type specificity of mitochondrial dynamics. Int J Biochem Cell B 41: 1928–1939.    
  • 19. Palmer CS, Osellame LD, Stojanovski D, et al. (2011) The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Cell Signal 23: 1534–1545.    
  • 20. Chen H, McCaffery JM, Chan DC (2007) Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum. Cell 130: 548–562.    
  • 21. Twig G, Elorza A, Molina AJ, et al. (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433–446.    
  • 22. Meeusen S, DeVay R, Block J, et al. (2006) Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127: 383–395.    
  • 23. Liesa M, Palacín M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89: 799–845.    
  • 24. Alexander C, Votruba M, Pesch U, et al. (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26: 211–215.    
  • 25. Detmer S, Chan D (2007) Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8: 870–879.    
  • 26. Ono T, Isobe K, Nakada K, et al. (2001) Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria. Exp Neurol 28: 272–275.
  • 27. Delettre C, Lenaers G, Griffoin JM, et al. (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26: 207–210.    
  • 28. Hudson G, Amati-Bonneau P, Blakely EL, et al. (2008) Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain 131: 329–337.    
  • 29. Uo T, Dworzak J, Kinoshita C, et al. (2009) Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons. Exp Neurol 218: 274–285.    
  • 30. Ishihara N, Nomura M, Jofuku A, et al. (2009) Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat Cell Biol 11: 958–966.    
  • 31. Darshi M, Mendiola VL, Mackey MR, et al. (2011) ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J Biol Chem 286: 2918–2932.    
  • 32. Koch A, Yoon Y, Bonekamp NA, et al. (2005) A Role for Fis1 in Both Mitochondrial and Peroxisomal Fission in Mammalian Cells. Mol Biol Cell 16: 5077–5086.    
  • 33. Serasinghe M, Yoon Y (2008) The mitochondrial outer membrane protein hFis1 regulates mitochondrial morphology and fission through self-interaction. Exp Cell Res 314: 3494–3507.    
  • 34. Otera H, Wang C, Cleland MM, et al. (2010) Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol 191: 1141–1158.    
  • 35. Knott AB, Perkins G, Schwarzenbacher R, et al. (2008) Mitochondrial fragmentation in neurodegeneration. Nat Rev Neurosci 9: 505–518.    
  • 36. Niemann A, Ruegg M, Padula VL, et al. (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.    
  • 37. Wagner KM, R ¨ uegg M, Niemann A, et al. (2009) Targeting and function of the mitochondrial fission factor GDAP1 are dependent on its tail-anchor. PloS One 4: e5160.    
  • 38. Chen H, Detmer SA, Ewald AJ, et al. (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160: 189–200.    
  • 39. Wakabayashi J, Zhang Z, Wakabayashi N, et al. (2009) The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol 186: 805–816.    
  • 40. Chu CT (2019) Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases. Neurobiol Dis 122: 23–34.    
  • 41. Kageyama Y, Zhang Z, Roda R, et al. (2012) Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol 197: 535–551.    
  • 42. Lutz AK, Exner N, Fett ME, et al. (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284: 22938–22951.    
  • 43. Matsuda N, Sato S, Shiba K, et al. (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189: 211–221.    
  • 44. Narendra DP, Jin SM, Tanaka A, et al. (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8: e1000298.    
  • 45. Zhu J, Dagda RK, CHu CT (2011) Monitoring mitophagy in neuronal cell cultures. Methods Mol Biol 793: 325–339.    
  • 46. Knott AB, Bossy-Wetzel E (2009) Impairing the Mitochondrial Fission and Fusion Balance: A New Mechanism of Neurodegeneration. Ann N Y Acad Sci 1147: 283–292.
  • 47. Martin LJ (2010) Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases. Pharmaceuticals 3: 839–915.    
  • 48. Corrado M, Scorrano L, Campello S (2012) Mitochondrial Dynamics in Cancer and Neurodegenerative and Neuroinflammatory Disease. Int J Cell Biol 2012.
  • 49. Su B, Wang X, Zheng L, et al. (2010) Abnormal mitochondrial dynamics and neurodegenerative diseases. Biochim Biophys Acta 1802: 135–142.    
  • 50. Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39: 889–909.    
  • 51. Chang D, Nalls MA, Hallgr ´ ımsd ´ ottir IB, et al. (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nat Genet 49: 1511.    
  • 52. Olanow C, Tatton W (1999) Etiology and pathogenesis of Parkinson's disease. Annu Rev Neurosci 22: 123–144.    
  • 53. Koh H, Chung J (2010) PINK1 and Parkin to control mitochondria remodeling. Anat Cell Biol 43: 179–184.    
  • 54. Narendra D, Tanaka A, Suen DF, et al. (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183: 795–803.    
  • 55. Billingsley KJ, Barbosa IA, Bandr ´ es-Ciga S, et al. (2019) Mitochondria function associated genes contribute to Parkinson's Disease risk and later age at onset. NPJ Parkinson's Dis 5: 8.    
  • 56. Panayiotou C, Solaroli N, Johansson M, et al. (2010) Evidence of an intact N-terminal translocation sequence of human mitochondrial adenylate kinase 4. Int J Biochem Cell Biol 42: 62–69.    
  • 57. Sai Y, Zou Z, Peng K, et al. (2012) The Parkinson's disease-related genes act in mitochondrial homeostasis. Neurosci Biobehav Rev 36: 2034–2043.    
  • 58. Perier C, Vila M (2012) Mitochondrial biology and Parkinson's disease. Cold Spring Harb Perspect Med 2: a009332.
  • 59. Comellas G, Lemkau LR, Nieuwkoop AJ, et al. (2011) Structured regions of α -synuclein fibrils include the early-onset Parkinson's disease mutation sites. J Mol Biol 411: 881–895.    
  • 60. Ulmer TS, Bax A (2005) Comparison of structure and dynamics of micelle-bound human α -synuclein and Parkinson disease variants. J Biol Chem 280: 43179–43187.    
  • 61. Nakamura K, Nemani VM, Azarbal F, et al. (2011) Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein α -synuclein. J Biol Chem 286: 20710–20726.    
  • 62. Mori H, Kondo T, Yokochi M, et al. (1998) Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology 51: 890–892.    
  • 63. Mizuno Y, Hattori N, Yoshino H, et al. (2006) Progress in familial Parkinson's disease. In Parkinson's Disease and Related Disorders, 191–204, Springer.
  • 64. Lodi R, Tonon C, Valentino M, et al. (2004) Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy. Ann Neurol 56: 719–723.    
  • 65. Mayorov V, Lowrey A, Biousse V, et al. (2008) Mitochondrial oxidative phosphorylation in autosomal dominant optic atrophy. BMC Biochem 9: 22.    
  • 66. Zanna C, Ghelli A, Porcelli AM, et al. (2008) OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131: 352–367.    
  • 67. Krajewski K, Lewis R, Fuerst D, et al. (2000) Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. Brain 44: 1299–1304.
  • 68. Berger P, Young P, Suter U (2002) Molecular cell biology of Charcot-Marie-Tooth disease. Neurogenetics 4: 1–15.    
  • 69. Baloh R, Schmidt R, Pestronk A, et al. (2007) Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci 27: 422–430.    
  • 70. Züchner S, Vance J (2006) Molecular genetics of autosomal-dominant axonal Charcot-Marie-Tooth disease. Neuromolecular Med 8: 63–74.    
  • 71. Sme F (2010) MFN2 mutations cause severe phenotypes in most patients with CMT2A. Neurology 125: 245–256.
  • 72. Cerveny K, Tamura Y (2007) Regulation of mitochondrial fusion and division. Trends Cell Biol 17: 563–569.    
  • 73. Poole AC, Thomas RE, Andrews LA, et al. (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105: 1638–1643.    
  • 74. Yang Y, Ouyang Y, Yang L, et al. (2008) Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A 105: 7070–7075.    
  • 75. Valente EM, Abou-Sleiman PM, Caputo V, et al. (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304: 1158–1160.    
  • 76. Rothfuss O, Fischer H, Hasegawa T, et al. (2009) Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair. Hum Mol Genet 18: 3832–3850.    
  • 77. Mortiboys H, Thomas KJ, Koopman WJ, et al. (2008) Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol 64: 555–565.    
  • 78. Büttner S, Bitto A, Ring J, et al. (2008) Functional mitochondria are required for α -synuclein toxicity in aging yeast. J Biol Chem 283: 7554–7560.    
  • 79. Banerjee K, Sinha M, Pham CLL, et al. (2010) α -Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson's disease. FEBS Lett 584: 1571–1576.    
  • 80. Yao C, El Khoury R, Wang W, et al. (2010) LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease. Neurobiol Dis 40: 73–81.    
  • 81. Wang X, Yan MH, Fujioka H, et al. (2012) LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 21: 1931–1944.    
  • 82. Pich S, Bach D, Briones P, 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.    
  • 83. Detmer SA, Chan DC (2007) Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J Cell Biol 176: 405–414.    
  • 84. Niemann A, Berger P, Suter U (2006) Pathomechanisms of Mutant Proteins in Charcot-Marie-Tooth Disease. NeuroMolecular Med 8: 217–242.    
  • 85. Noack R, Frede S, Albrecht P, et al. (2012) Charcot–Marie–Tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential. Hum Mol Genet 21: 150–162.    
  • 86. Cho D, Nakamura T, Fang J, et al. (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324: 102–105.    
  • 87. Olichon A, Baricault L, Gas N (2003) Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem 278: 7743–7746.    
  • 88. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443: 787.    
  • 89. Wang X, Wang W, Li L, et al. (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer's disease. Biochim Biophys Acta 1842: 1240–1247.    
  • 90. Smith MA, Rottkamp CA, Nunomura A, et al. (2000) Oxidative stress in Alzheimer's disease. Biochim Biophys Acta 1502: 139–144.    
  • 91. Hirai K, Aliev G, Nunomura A, et al. (2001) Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 21: 3017–3023.    
  • 92. Sun A, Chen Y (1998) Oxidative stress and neurodegenerative disorders. J Biomed Sci 5: 401–414.    
  • 93. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39: 73–82.    
  • 94. Wang X, Su B, Fujioka H, et al. (2008) Dynamin-like protein 1 reduction underlies mitochondrial morphologyanddistributionabnormalitiesinfibroblastsfromsporadicAlzheimer'sdiseasepatients. Am J Pathol 173: 470–482.    
  • 95. Wang X, Su B, Siedlak SL, et al. (2008) Amyloid- β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci 105: 19318–19323.    
  • 96. Martin M, Hurd D, Saxton W (1999) Kinesins in the nervous system. Cell Mol Life Sci 56: 200–216.    
  • 97. Schnapp BJ, Reese TS (1989) Dynein is the motor for retrograde axonal transport of organelles. Proc Natl Acad Sci U S A 86: 1548–1552.    
  • 98. Tabb JS, Molyneaux BJ, Cohen DL, et al. (1998) Transport of ER vesicles on actin filaments in neurons by myosin V. J Cell Sci 111: 3221–3234.
  • 99. Ligon LA, Steward O (2000) Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of culture hippocampal neurons. Journal Comp Neur 427: 351–361.    
  • 100. Hirokawa N (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279: 519–526.    
  • 101. Gross SP (2004) Hither and yon: A review of bi-directional microtubule-based transport. Phys Biol 1: R1–R11.    
  • 102. Ligon LA, Tokito M, Finklestein JM, et al. (2004) A direct interaction between cytoplasmic dynein and kinesin I may coordinate motor activity. J Biol Chem 279: 19201–19208.    
  • 103. Stowers R, Megeath L, G ´ orska-Andrzejak J, et al. (2002) Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36: 1063–1077.    
  • 104. Guo X, Macleod G, Wellington A, et al. (2005) The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 47: 379–393.    
  • 105. Russo G, Louie K, Wellington A, et al. (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci 29: 5443–5455.    
  • 106. Koutsopoulos OS, Laine D, Osellame L, et al. (2010) Human miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks. Biochim Biophys Acta 1803: 564–574.    
  • 107. Wang X, Winter D, Ashrafi G, et al. (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147: 893–906.    
  • 108. Hsieh CH, Shaltouki A, Gonzalez AE, et al. (2016) Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson's disease. Cell Stem Cell 19: 709–724.    
  • 109. Baloh RH (2008) Mitochondrial dynamics and peripheral neuropathy. Neuroscientist 14: 12–18.    
  • 110. Misko A, Jiang S, Wegorzewska I, et al. (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30: 4232–4240.    
  • 111. Ikenaka K, Katsuno M, Kawai K, et al. (2012) Disruption of axonal transport in motor neuron diseases. Int J Mol Sci 13: 1225–1238.    
  • 112. Mandal A, Drerup CM (2019) Axonal transport and mitochondrial function in neurons. Front Cell Neurosci 13: 373.
  • 113. Ader NR (2016) Seeking an in vivo neuronal context for the PINK1/Parkin pathway. J Neurosci 36: 11165–11167.    
  • 114. Metaxakis A, Ploumi C, Tavernarakis N (2018) Autophagy in age-associated neurodegeneration. Cells 7: 37.    
  • 115. Rintoul GL, Reynolds IJ (2010) Mitochondrial trafficking and morphology in neuronal injury. Biochim Biophys Acta 1802: 143–150.    
  • 116. Chang DT, Reynolds IJ (2006) Mitochondrial trafficking and morphology in healthy and injured neurons. Prog Neurobiol 80: 241–268.    
  • 117. Weihofen A, Thomas K, Ostaszewski B, et al. (2009) Pink1 forms a multiprotein complex with miro and milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 48: 2045–2052.    
  • 118. Yang F, Jiang Q, Zhao J, et al. (2005) Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem 280: 17154–17162.    
  • 119. Lee H, Khoshaghideh F, Lee S, et al. (2006) Impairment of microtubule-dependent trafficking by overexpression of α-synuclein. European J Neurosci 24: 3153–3162.    
  • 120. Gillardon F (2009) Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability-A point of convergence in Parkinsonian neurodegeneration? J Neurochem 10: 1514–1522.
  • 121. Braak E, Sandmann-Keil D, Rüb U, et al. (2001) α -Synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei. Acta Neuropathol 101: 195–201.    
  • 122. Liu S, Sawada T, Lee S, et al. (2012) Parkinson's disease–associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet 8: e1002537.    
  • 123. Chu Y, Morfini GA, Langhamer LB, et al. (2012) Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. Brain 135: 2058–2073.    
  • 124. Abeliovich A, Gitler AD (2016) Defects in trafficking bridge Parkinson's disease pathology and genetics. Nature 539: 207.    
  • 125. Züchner S, Mersiyanova I, Muglia M, et al. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36: 449–451.    
  • 126. Patzk ´ o A, Shy ME (2011) Update on Charcot-Marie-Tooth Disease. Curr Neurol Neurosci Rep 11: 78–88.    
  • 127. Shy M (2004) Charcot-Marie-Tooth disease: An update. Curr Opin Neurol 17: 579–585.    
  • 128. Loiseau D, Chevrollier A, Verny C, et al. (2007) Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease. Ann Neurol 61: 315–323.    
  • 129. Stokin G, Lillo C, Falzone T, et al. (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer's diseases. Science 307: 1282–1288.    
  • 130. Wang X, Su B, Lee H (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 29: 9090–9103.    
  • 131. Vickers JC, King AE, Woodhouse A, et al. (2009) Axonopathy and cytoskeletal disruption in degenerative diseases of the central nervous system. Brain Res Bull 80: 217–223.    
  • 132. De Vos K, Chapman A, Tennant M, et al. (2007) Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 16: 2720–2728.    
  • 133. Shi P, Ström A, Gal J, et al. (2010) Effects of ALS-related SOD1 mutants on dynein- and KIF5-mediated retrograde and anterograde axonal transport. Biochim Biophys Acta 1802: 707–716.    
  • 134. Chang D, Rintoul G, Pandipati S, et al. (2006) Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 22: 388–400.    
  • 135. Trushina E, Dyer R, Badger J, et al. (2004) Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 24: 8195–8209.    
  • 136. Bach D, Pich S, Soriano FX (2003) Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism: a novel regulatory mechanism altered in obesity. J Biol Chem 278: 17190–17197.    
  • 137. Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280: 26185–26192.    
  • 138. Van Laar VS, Berman SB (2013) The interplay of neuronal mitochondrial dynamics and bioenergetics: implications for Parkinson's disease. Neurobiol Dis 51: 43–55.    
  • 139. Coskun P, Wyrembak J, Schriner SE, et al. (2012) A mitochondrial etiology of Alzheimer and Parkinson disease. Biochim Biophys Acta 1820: 553–564.    
  • 140. Ryan BJ, Hoek S, Fon EA, et al. (2015) Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci 40: 200–210.    
  • 141. Van Laar VS, Berman SB (2009) Mitochondrial dynamics in Parkinson's disease. Exp Neurol 218: 247–256.    
  • 142. Requejo-Aguilar R, Bolaños JP (2016) Mitochondrial control of cell bioenergetics in Parkinson's disease. Free Radic Biol Med 100: 123–137.    
  • 143. Abramov AY, Gegg M, Grunewald A, et al. (2011) Bioenergetic consequences of PINK1 mutations in Parkinson disease. PLoS One 6: e25622.    
  • 144. Lansbury PT, Lashuel HA (2006) A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 443: 774–779.    
  • 145. Jain S, Wood NW, Healy DG (2005) Molecular genetic pathways in Parkinson's disease: A review. Clin Sci 109: 355–364.    
  • 146. Winklhofer KF, Haass C (2010) Mitochondrial dysfunction in Parkinson's disease. Biochim Biophy Acta 1802: 29–44.    
  • 147. Chen C, Turnbull DM, Reeve AK (2019) Mitochondrial Dysfunction in Parkinson's Disease-Cause or Consequence? Biology 8: 38.    
  • 148. Diot A, Morten K, Poulton J (2016) Mitophagy plays a central role in mitochondrial ageing. Mamm Genome 27: 381–395.    
  • 149. Noda S, Sato S, Fukuda T, et al. (2019) Loss of Parkin contributes to mitochondrial turnover and dopaminergic neuronal loss in aged mice. Neurobiol Dis 136: 104717.
  • 150. Fivenson EM, Lautrup S, Sun N, et al. (2017) Mitophagy in neurodegeneration and aging. Neurochem Int 109: 202–209.    
  • 151. Ebrahimi-Fakhari D, Wahlster L, McLean PJ (2012) Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathol 124: 153–172.    
  • 152. Wang W, Wang X, Fujioka H, et al. (2016) Parkinson's disease–associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med 22: 54.    
  • 153. Singleton A, Farrer M, Johnson J, et al. (2003) α -Synuclein locus triplication causes Parkinson's disease. Science 302: 841–841.    
  • 154. Regev A, Silverman W, Shapiro E (2001) Representation and simulation of biochemical processes using the π-calculus process algebra. Pac Symp Biocomput, 459–470.
  • 155. Bonzanni N, Feenstra KA, Fokkink W, et al. (2009) What can formal methods bring to systems biology? In International Symposium on Formal Methods, Springer, 16–22.
  • 156. Theocharopoulou G, Giannakis K, Andronikos T (2015) The mechanism of splitting mitochondria in terms of membrane automata. In 2015 IEEE International Symposium on Signal Processing and Information Technology (ISSPIT) IEEE, 397–402.
  • 157. Theocharopoulou G, Vlamos P (2015) Modeling protein misfolding in Charcot–Marie–Tooth disease. In GeNeDis 2014, Springer, 91–102.
  • 158. Theocharopoulou G, Bobori C, Vlamos P (2017) Formal models of biological systems. In GeNeDis 2016, Springer, 325–338.
  • 159. Corona JC, Duchen MR (2015) Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets? J Bioenerg Biomembr 47: 89–99.    
  • 160. Kitada T, Asakawa S, Hattori N, et al. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605.    
  • 161. Healy DG, Falchi M, O'Sullivan SS, et al. (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol 7: 583–590.    
  • 162. Peng JY, Lin CC, Chen YJ, et al. (2011) Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics. PLoS Comput Biol 7: e1002212.    
  • 163. Tronstad KJ, Nooteboom M, Nilsson LI, et al. (2014) Regulation and quantification of cellular mitochondrial morphology and content. Curr Pharm Des 20: 5634–5652.    
  • 164. Zamponi N, Zamponi E, Cannas SA, et al. (2018) Mitochondrial network complexity emerges from fission/fusion dynamics. Sci Rep 8: 363.    
  • 165. Shah SI, Paine JG, Perez C, et al. (2019) Mitochondrial fragmentation and network architecture in degenerative diseases. PloS One 14: e0223014.    
  • 166. Toglia P, Demuro A, Mak DOD, et al. (2018) Data-driven modeling of mitochondrial dysfunction in Alzheimer's disease. Cell Calcium 76: 23–35.    
  • 167. Dukes AA, Bai Q, Van Laar VS, et al. (2016) Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP+ exposure. Neurobiol Dis 95: 238–249.    
  • 168. Alexiou A, Vlamos P (2012) Evidence for early identification of Alzheimer's disease. In arXiv preprint arXiv:1209.4223
  • 169. Lundkvist J, Naslund J (2007) Gamma-secretase: A complex target for Alzheimer's disease. Curr Opin Pharmacol 7: 112–118.    
  • 170. Evin G, Kenche V (2007) BACE inhibitors as potential therapeutics for Alzheimer's disease. Recent Pat CNS Drug Discov 2: 188–199.
  • 171. Alexiou A, Vlamos P, Rekkas J (2011) Modeling the mitochondrial dysfunction in neurogenerative diseases due to high H+ concentration. Bioinformation 6: 173–175.    
  • 172. Miller KE, Sheetz MP (2004) Axonal mitochondrial transport and potential are correlated. J Cell Sci 117: 2791–2804.    
  • 173. Oliveira JMA (2011) Techniques to investigate neuronal mitochondrial function and its pharmacological modulation. Curr Drug Targets 12: 762–773.    
  • 174. Twig G, Hyde B, Shirihai OS (2008) Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 1777: 1092–1097.    
  • 175. Onyango IG, Dennis J, Khan SM (2016) Mitochondrial dysfunction in Alzheimer's disease and the rationale for bioenergetics based therapies. Aging Dis 7: 201–214.    

 

Reader Comments

your name: *   your email: *  

© 2020 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved