Mitochondrial dysfunction is a converging point of multiple pathological pathways in amyotrophic lateral sclerosis

Journal of Alzheimer's Disease

Volumn 20, Issue SUPPL.2, 2010, Pages

  Shi, Ping ^a   Wei, Yanming ^a   Zhang, Jiayu ^a   Gal, Jozsef ^a   Zhu, Haining ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Amyotrophic lateral sclerosis; autophagy; axonal transport; mitochondrial dynamics; mitochondrial function; mutant SOD1

Indexed keywords

CALCIUM; CASPASE 3; CASPASE 8; INTERLEUKIN 1BETA CONVERTING ENZYME; KINESIN; NEUROTROPHIN RECEPTOR P75; PROTEIN BAD; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; SUPEROXIDE DISMUTASE; UNCOUPLING PROTEIN 1; X LINKED INHIBITOR OF APOPTOSIS;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; AUTOPHAGY; BIOENERGY; CALCIUM HOMEOSTASIS; CALCIUM TRANSPORT; DENERVATION; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DROSOPHILA; ENZYME ACTIVATION; GENE OVEREXPRESSION; HUMAN; MEMBRANE FUSION; MICROGLIA; MITOCHONDRION; MORPHOLOGY; MOTONEURON; NEUROPATHY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN TRANSPORT; RESPIRATORY CHAIN; RETROGRADE NERVE FIBER TRANSPORT; REVIEW; SCHWANN CELL; SPASTIC PARAPLEGIA; TRANSGENIC MOUSE;

EID: 77956224840     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2010-100366     Document Type: Review

References (159)

1. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62.
2. Bruijn LI, Miller TM, Cleveland DW (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27, 723-749.
3. Yang Y, Hentati A, Deng HX, Dabbagh O, Sasaki T, Hirano M, Hung WY, Ouahchi K, Yan J, Azim AC, Cole N, Gascon G, Yagmour A, Ben-Hamida M, Pericak-Vance M, Hentati F, Siddique T (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet 29, 160-165.
4. Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, Miyamoto N, Showguchi-Miyata J, Okada Y, Singaraja R, Figlewicz DA, Kwiatkowski T, Hosler BA, Sagie T, Skaug J, Nasir J, Brown RH, Jr., Scherer SW, Rouleau GA, Hayden MR, Ikeda JE (2001) A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet 29, 166-173.
5. Nishimura AL, Mitne-Neto M, Silva HCA, Richieri-Costa Middleton S, Cascio D, Kok F, Oliveira JRM, Gilling- water T, Webb J, Skehel P, Zatz M (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Human Genet 75, 822-831.
6. Chen Y-Z, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, Dierick I, Abel A, Kennerson ML, Rabin BA, Nicholson GA, Auer-Grumbach M, Wagner K, De Jonghe P, Griffin JW, Fischbeck KH, Timmerman V, Cornblath DR, Chance PF (2004) DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Human Genet 74, 1128-1135.
7. Munch C, Sedlmeier R, Meyer T, Homberg V, Sperfeld AD, Kurt A, Prudlo J, Peraus G, Hanemann CO, Stumm G, Lu- dolph AC (2004) Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology 63, 724-726.
8. Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH, Jr., Hardiman O (2006) ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet 38, 411-413.
9. Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40, 572-574.
10. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogel J, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672.
11. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Gane- salingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gal- lo JM, Miller CC, Shaw CE (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208-1211.
12. Kwiatkowski TJ, Jr., Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH, Jr. (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amy- otrophic lateral sclerosis. Science 323, 1205-1208.
13. Chu CT (2010) Tickled PINK1: mitochondrial homeostasis and autophagy in recessive Parkinsonism. Biochim Biophys Acta 1802, 20-28.
14. Manfredi G, Xu Z (2005) Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. Mitochondrion 5, 77-87.
15. Crapo JD, Oury T, Rabouille C, Slot JW, Chang LY (1992) Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. Proc Natl Acad Sci U SA 89, 1040510409.
16. Kikuchi H, Almer G, Yamashita S, Guegan C, Nagai M, Xu Z, Sosunov AA, McKhann GM, 2nd, Przedborski S (2006) Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model. Proc Natl Acad Sci USA 103, 6025-6030.
17. Okado-Matsumoto A, Fridovich I (2001) Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn- SOD in mitochondria. J Biol Chem 276, 38388-38393.
18. Sturtz LA, Diekert K, Jensen LT, Lill R, Culotta VC (2001) A fraction of yeast Cu,Zn-superoxide dismutase and its met- allochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J Biol Chem 276, 38084-38089.
19. Atkin JD, Farg MA, Turner BJ, Tomas D, Lysaght JA, Nunan J, Rembach A, Nagley P, Beart PM, Cheema SS, Horne MK (2006) Induction of the unfolded protein response in familial amyotrophic lateral sclerosis and association of protein- disulfide isomerase with superoxide dismutase 1. J Biol Chem 281, 30152-30165.
20. Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, Noguchi T, Matsuzawa A, Takeda K, Ichijo H (2008) ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev 22, 1451-1464.
21. Saxena S, Cabuy E, Caroni P (2009) A role for motoneu- ron subtype-selective ER stress in disease manifestations of FALS mice. Nat Neurosci 12, 627-636.
22. Higgins CM, Jung C, Ding H, Xu Z (2002) Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS. JNeurosci 22, RC215.
23. Vijayvergiya C, Beal MF, Buck J, Manfredi G (2005) Mutant superoxide dismutase 1 forms aggregates in the brain mitochondrial matrix of amyotrophic lateral sclerosis mice. J Neurosci 25, 2463-2470.
24. Vande Velde C, Miller TM, Cashman NR, Cleveland DW (2008) Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria. Proc Natl Acad Sci USA 105, 4022-4027.
25. Kawamata H, Manfredi G (2008) Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria. Hum Mol Genet 17, 33033317.
26. Field LS, Furukawa Y, O'Halloran TV, Culotta VC (2003) Factors controlling the uptake of yeast copper/zinc superox- ide dismutase into mitochondria. J Biol Chem 278, 2805228059. .
27. Son M, Puttaparthi K, Kawamata H, Rajendran B, Boyer PJ, Manfredi G, Elliott JL (2007) Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology. Proc Natl Acad Sci U SA 104, 6072-6077.
28. Liu J, Lillo C, Jonsson PA, Vande Velde C, Ward CM, Miller TM, Subramaniam JR, Rothstein JD, Marklund S, Andersen PM, Brannstrom T, Gredal O, Wong PC, Williams DS, Cleveland DW (2004) Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43, 5-17.
29. Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar deg-eneration of mitochondria. Neuron 14, 1105-1116.
30. Kong J, Xu Z (1998) Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J Neurosci 18, 3241-3250.
31. Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM (1999) Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 46, 787-790.
32. Jung C, Higgins CM, Xu Z (2002) A quantitative histochem- ical assay for activities of mitochondrial electron transport chain complexes in mouse spinal cord sections. J Neurosci Methods 114, 165-172.
33. Bowling AC, Schulz JB, Brown RH, Jr., Beal MF (1993) Superoxide dismutase activity, oxidative damage, and mito- chondrial energy metabolism in familial and sporadic amy- otrophic lateral sclerosis. JNeurochem 61, 2322-2325.
34. Ferri A, Cozzolino M, Crosio C, Nencini M, Casciati A, Gralla EB, Rotilio G, Valentine JS, Carri MT (2006) Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials. Proc Natl Acad Sci U S A 103, 13860-13865.
35. Krieger C, Lanius RA, Pelech SL, Shaw CA (1996) Amy- otrophic lateral sclerosis: the involvement of intracellular Ca2+ and protein kinase C. Trends Pharmacol Sci 17, 114120.
36. Kruman, II, Pedersen WA, Springer JE, Mattson MP (1999) ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis. Exp Neurol 160, 28-39.
37. Carri MT, Ferri A, Battistoni A, Famhy L, Gabbianelli R, Poccia F, Rotilio G (1997) Expression of a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells. FEBSLett 414, 365-368.
38. Pasinelli P, Belford ME, Lennon N, Bacskai BJ, Hyman BT, Trotti D, Brown RH, Jr. (2004) Amyotrophic lateral sclerosis- associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43, 19-30.
39. Kirkinezos IG, Bacman SR, Hernandez D, Oca-Cossio J, Arias LJ, Perez-Pinzon MA, Bradley WG, Moraes CT (2005) Cytochrome c association with the inner mitochondrial membrane is impaired in the CNS of G93A-SOD1 mice. J Neu- rosci 25, 164-172.
40. Takeuchi H, Kobayashi Y, Ishigaki S, Doyu M, Sobue G (2002) Mitochondrial localization of mutant superoxide dis- mutase 1 triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis. J Biol Chem 277, 50966-50972.
41. Dal Canto MC, Gurney ME (1995) Neuropathological changes in two lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis (FALS). Brain Res 676, 25-40.
42. Jaarsma D, Haasdijk ED, Grashorn JA, Hawkins R, van Dui- jn W, Verspaget HW, London J, Holstege JC (2000) Human Cu/Zn superoxide dismutase (SOD1) overexpression in mice causes mitochondrial vacuolization, axonal degeneration, and premature motoneuron death and accelerates mo- toneuron disease in mice expressing a familial amyotrophic lateral sclerosis mutant SOD1. Neurobiol Dis 7, 623-643.
43. Sasaki S, Iwata M (1996) Ultrastructural study of synapses in the anterior horn neurons of patients with amyotrophic lateral sclerosis. Neurosci Lett 204, 53-56.
44. Hirano A, Nakano I, Kurland LT, Mulder DW, Holley PW, Saccomanno G(1984) Fine structural study of neurofibrillary changes in a family with amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43, 471-480.
45. Sotelo-Silveira JR, Lepanto P, Elizondo V, Horjales S, Pala- cios F, Martinez-Palma L, Marin M, Beckman JS, Barbeito L (2009) Axonal mitochondrial clusters containing mutant SOD1 in transgenic models of ALS. Antioxid Redox Signal 11, 1535-1545.
46. Raimondi A, Mangolini A, Rizzardini M, Tartari S, Massari S, Bendotti C, Francolini M, Borgese N, Cantoni L, Pietrini G (2006) Cell culture models to investigate the selective vulnerability ofmotoneuronal mitochondria to familial ALS- linked G93ASOD1. Eur J Neurosci 24, 387-399.
47. Menzies FM, Cookson MR, Taylor RW, Turnbull DM, Chrzanowska-Lightowlers ZM, Dong L, Figlewicz DA, Shaw PJ (2002) Mitochondrial dysfunction in a cell culture model of familial amyotrophic lateral sclerosis. Brain 125, 1522-1533.
48. Higgins CM, Jung C, Xu Z (2003) ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci 4, 16.
49. Reiner A, Medina L, Figueredo-Cardenas G, Anfinson S (1995) Brainstem motoneuron pools that are selectively resistant in amyotrophic lateral sclerosis are preferentially enriched in parvalbumin: evidence from monkey brainstem for a calcium-mediated mechanism in sporadic ALS. Exp Neurol 131, 239-250.
50. Damiano M, Starkov AA, Petri S, Kipiani K, Kiaei M, Mat- tiazzi M, Flint Beal M, Manfredi G (2006) Neural mitochon- drial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J Neurochem 96, 1349-1361.
51. Jaiswal MK, Zech WD, Goos M, Leutbecher C, Ferri A, Zippelius A, Carri MT, Nau R, Keller BU (2009) Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease. BMC Neurosci 10, 64.
52. Wang X, Schwarz TL (2009) The mechanism of Ca2+ -dependent regulation of kinesin-mediated mitochondrial motility. Cell 136, 163-174.
53. Chang DT, Honick AS, Reynolds IJ (2006) Mitochondrial trafficking to synapses in cultured primary cortical neurons. J Neurosci 26, 7035-7045.
54. Yi M, Weaver D, Hajnoczky G (2004) Control of mitochon- drial motility and distribution by the calcium signal: a home- ostatic circuit. J Cell Biol 167, 661-672.
55. Guegan C, Vila M, Rosoklija G, Hays AP, Przedborski S (2001) Recruitment of the mitochondrial-dependent apoptot- ic pathway in amyotrophic lateral sclerosis. J Neurosci 21, 6569-6576.
56. Vukosavic S, Dubois-Dauphin M, Romero N, Przedborski S (1999) Bax and Bcl-2 interaction in a transgenic mouse model offamilial amyotrophic lateral sclerosis. J Neurochem 73, 2460-2468.
57. Ishigaki S, Liang Y, Yamamoto M, Niwa J, Ando Y, Yoshi- hara T, Takeuchi H, Doyu M, Sobue G (2002) X-Linked inhibitor of apoptosis protein is involved in mutant SOD1- mediated neuronal degeneration. J Neurochem 82, 576-584.
58. Li M, Ona VO, Guegan C, Chen M, Jackson-Lewis V, Andrews LJ, Olszewski AJ, Stieg PE, Lee JP, Przedborski S, Friedlander RM (2000) Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 288, 335-339.
59. Pasinelli P, Borchelt DR, Houseweart MK, Cleveland DW, Brown RH, Jr. (1998) Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proc Natl Acad Sci USA 95, 15763-15768.
60. Pasinelli P, Houseweart MK, Brown RH, Jr., Cleveland DW (2000) Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 97, 13901-13906.
61. Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Fer- rante RJ, Przedborski S, Kristal BS, Friedlander RM (2002) Minocycline inhibits cytochrome c release and delays progression ofamyotrophic lateral sclerosis in mice. Nature 417, 74-78.
62. Kostic V, Jackson-Lewis V, de Bilbao F, Dubois-Dauphin M, Przedborski S (1997) Bcl-2: prolonging life in a trans- genic mouse model of familial amyotrophic lateral sclerosis. Science 277, 559-562.
63. Martin LJ, Gertz B, Pan Y, Price AC, Molkentin JD, Chang Q (2009) The mitochondrial permeability transition pore in motor neurons: Involvement in the pathobiology of ALS mice. Exp Neurol 218, 333-346.
64. Gordon PH, Moore DH, Miller RG, Florence JM, Verhei- jde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, Neville HE, Boylan K, Mozaffar T, Belsh JM, Ravits J, Bedlack RS, Graves MC, McCluskey LF, Barohn RJ, Tandan R (2007) Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 6, 1045-1053.
65. Gould TW, Buss RR, Vinsant S, Prevette D, Sun W, Knudson CM, Milligan CE, Oppenheim RW (2006) Complete dissociation of motor neuron death from motor dysfunction by Bax deletion in a mouse model of ALS. J Neurosci 26, 8774-8786.
66. Fischer LR, Culver DG, Tennant P, Davis AA, Wang M, Castellano-Sanchez A, Khan J, Polak MA, Glass JD (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 185, 232-240.
67. Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2, 50-56.
68. Zhang B, Tu P, Abtahian F, Trojanowski JQ, Lee VM (1997) Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J Cell Biol 139, 1307-1315.
69. Reid E, Kloos M, Ashley-Koch A, Hughes L, Bevan S, Svenson IK, Graham FL, Gaskell PC, Dearlove A, Pericak- Vance MA, Rubinsztein DC, Marchuk DA (2002) A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). Am J Hum Genet 71, 1189-1194.
70. Puls I, Jonnakuty C, LaMonte BH, Holzbaur EL, Tokito M, Mann E, Floeter MK, Bidus K, Drayna D, Oh SJ, Brown RH, Jr., Ludlow CL, Fischbeck KH (2003) Mutant dynactin in motor neuron disease. Nat Genet 33, 455-456.
71. LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascano J, Tokito M, Van Winkle T, Howland DS, Holzbaur EL (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34, 715-727.
72. Hafezparast M, Klocke R, Ruhrberg C, Marquardt A, Ahmad-Annuar A, Bowen S, Lalli G, Witherden AS, Hum-merich H, Nicholson S, Morgan PJ, Oozageer R, Priestley JV, Averill S, King VR, Ball S, Peters J, Toda T, Yamamoto A,Hiraoka Y, Augustin M, Korthaus D, Wattler S, Wabnitz P, Dickneite C, Lampel S, Boehme F, Peraus G, Popp A, Rudelius M, Schlegel J, Fuchs H, Hrabe de Angelis M, Schi- avo G, Shima DT, Russ AP, Stumm G, Martin JE, Fisher EM (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300, 808-812.
73. Chen XJ, Levedakou EN, Millen KJ, Wollmann RL, Soliven B,Popko B (2007) Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J Neurosci 27, 14515-14524.
74. Lai C, Lin X, Chandran J, Shim H, Yang WJ, Cai H (2007) The G59S mutation in p150(glued) causes dysfunction of dynactin in mice. J Neurosci 27, 13982-13990.
75. Teuling E, van Dis V, Wulf PS, Haasdijk ED, Akhmanova A, Hoogenraad CC, Jaarsma D (2008) A novel mouse model with impaired dynein/dynactin function develops amyotrophic lateral sclerosis (ALS)-like features in motor neurons and improves lifespan in SOD1-ALS mice. HumMol Genet 17, 2849-2862.
76. Laird FM, Farah MH, Ackerley S, Hoke A, Maragakis N, Rothstein JD, Griffin J, Price DL, Martin LJ, Wong PC (2008) Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular trafficking. J Neurosci 28, 1997-2005.
77. Breuer AC, Lynn MP, Atkinson MB, Chou SM, Wilbourn AJ, Marks KE, Culver JE, Fleegler EJ (1987) Fast axonal transport in amyotrophic lateral sclerosis: an intra-axonal organelle traffic analysis. Neurology 37, 738-748.
78. Breuer AC, Atkinson MB (1988) Fast axonal transport alterations in amyotrophic lateral sclerosis (ALS) and in parathyroid hormone (PTH)-treated axons. Cell Motil Cytoskeleton 10, 321-330.
79. Collard JF, Cote F, Julien JP (1995) Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 375, 61-64.
80. Sasaki S, Iwata M (1996) Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotroph- ic lateral sclerosis. Neurology 47, 535-540.
81. Ligon LA, LaMonte BH, Wallace KE, Weber N, Kalb RG, Holzbaur EL (2005) Mutant superoxide dismutase disrupts cytoplasmic dynein in motor neurons. Neuroreport 16, 533536.
82. Parkhouse WS, Cunningham L, McFee I, Miller JM, Whitney D, Pelech SL, Krieger C (2008) Neuromuscular dysfunction in the mutant superoxide dismutase mouse model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9, 24-34.
83. Kieran D, Hafezparast M, Bohnert S, Dick JR, Martin J, Schiavo G, Fisher EM, Greensmith L (2005) A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J Cell Biol 169, 561-567.
84. Teuchert M, Fischer D, Schwalenstoecker B, Habisch HJ, Bockers TM, Ludolph AC (2006) A dynein mutation attenuates motor neuron degeneration in SOD1(G93A) mice. Exp Neurol 198, 271-274.
85. Zhang F, Strom AL, Fukada K, Lee S, Hayward LJ, Zhu H (2007) Interaction between familial amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants and the dynein complex. J Biol Chem 282, 16691-16699.
86. Strom AL, Shi P, Zhang F, Gal J, Kilty R, Hayward LJ, Zhu H (2008) Interaction of amyotrophic lateral sclerosis (ALS)- related mutant copper-zinc superoxide dismutase with the dynein-dynactin complex contributes to inclusion formation. J Biol Chem 283, 22795-22805.
87. Tateno M, Kato S, Sakurai T, Nukina N, Takahashi R, Araki T (2009) Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3. Hum Mol Genet 18, 942-955.
88. Landers JE, Melki J, Meininger V, Glass JD, van den Berg LH, van Es MA, Sapp PC, van Vught PW, McKenna-Yasek DM, Blauw HM, Cho TJ, Polak M, Shi L, Wills AM, Broom WJ, Ticozzi N, Silani V, Ozoguz A, Rodriguez-Leyva I, Veldink JH, Ivinson AJ, Saris CG, Hosler BA, Barnes-Nessa A, Couture N, Wokke JH, Kwiatkowski TJ, Jr., Ophoff RA, Cronin S, Hardiman O, Diekstra FP, Leigh PN, Shaw CE, Simpson CL, Hansen VK, Powell JF, Corcia P, Salachas F, Heath S, Galan P, Georges F, Horvitz HR, Lathrop M, Purcell S, Al-Chalabi A, Brown RH, Jr. (2009) Reduced expression ofthe Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 106, 9004-9009.
89. Dupuis L, de Tapia M, Rene F, Lutz-Bucher B, Gordon JW, Mercken L, Pradier L, Loeffler JP (2000) Differential screening of mutated SOD1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons. Neurobiol Dis 7, 274-285.
90. Perlson E, Jeong GB, Ross JL, Dixit R, Wallace KE, Kalb RG, Holzbaur EL (2009) A switch in retrograde signaling from survival to stress in rapid-onset neurodegeneration. J Neurosci 29, 9903-9917.
91. Tortarolo M, Veglianese P, Calvaresi N, Botturi A, Rossi C, Giorgini A, Migheli A, Bendotti C (2003) Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol Cell Neurosci 23, 180-192.
92. Ackerley S, Grierson AJ, Banner S, Perkinton MS, Brown- lees J, Byers HL, Ward M, Thornhill P, Hussain K, Waby JS, Anderton BH, Cooper JD, Dingwall C, Leigh PN, Shaw CE, Miller CC (2004) p38alpha stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis. Mol Cell Neurosci 26, 354-364.
93. De Vos K, Severin F, Van Herreweghe F, Vancompernolle K, Goossens V, Hyman A, Grooten J (2000) Tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria. J Cell Biol 149, 1207-1214.
94. Morfini G, Pigino G, Szebenyi G, You Y, Pollema S, Brady ST (2006) JNK mediates pathogenic effects of polyglutamine- expanded androgen receptor on fast axonal transport. Nat Neurosci 9, 907-916.
95. Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118, 5411-5419.
96. Goldstein AY, Wang X, Schwarz TL (2008) Axonal transport and the delivery of pre-synaptic components. Curr Opin Neurobiol 18, 495-503.
97. Shepherd GM, Harris KM (1998) Three-dimensional structure and composition of CA3-CA1 axons in rat hippocam- pal slices: implications for presynaptic connectivity and compartmentalization. J Neurosci 18, 8300-8310.
98. Rowland KC, Irby NK, Spirou GA (2000) Specialized synapse-associated structures within the calyx of Held. J Neurosci 20, 9135-9144.
99. Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119, 873-887.
100. Tanaka Y, Kanai Y, Okada Y, Nonaka S, Takeda S, Harada A, Hirokawa N (1998) Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93, 1147-1158.
101. Nangaku M, Sato-Yoshitake R, Okada Y, Noda Y, Takemura R, Yamazaki H, Hirokawa N (1994) KIF1B, a novel micro- tubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79, 1209-1220.
102. Zhang Y, Oko R, van der Hoorn FA (2004) Rat kinesin light chain 3 associates with spermatid mitochondria. Dev Biol 275, 23-33.
103. Varadi A, Johnson-Cadwell LI, Cirulli V, Yoon Y, Allan VJ, Rutter GA (2004) Cytoplasmic dynein regulates the subcel- lular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1. J Cell Sci 117, 4389-4400.
104. Glater EE, Megeath LJ, Stowers RS, Schwarz TL (2006) Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol 173, 545-557.
105. Fransson S, Ruusala A, Aspenstrom P (2006) The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking. Biochem Biophys Res Commun 344, 500-510.
106. Guo X, Macleod GT, Wellington A, Hu F, Panchumarthi S, Schoenfield M, Marin L, Charlton MP, Atwood HL, Zins- maier KE (2005) The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 47, 379-393.
107. Fransson A, Ruusala A, Aspenstrom P (2003) Atypical Rho GTPases have roles in mitochondrial homeostasis and apop- tosis. J Biol Chem 278, 6495-6502.
108. Beck M, Brickley K, Wilkinson HL, Sharma S, Smith M, Chazot PL, Pollard S, Stephenson FA (2002) Identification, molecular cloning, and characterization of a novel GABAA receptor-associated protein, GRIF-1. J Biol Chem 277, 30079-30090.
109. Iyer SP, Akimoto Y, Hart GW (2003) Identification and cloning of a novel family of coiled-coil domain proteins that interact with O-GlcNAc transferase. J Biol Chem 278, 53995409.
110. Brickley K, Smith MJ, Beck M, Stephenson FA (2005) GRIF- 1 and OIP106, members of a novel gene family of coiled- coil domain proteins: association in vivo and in vitro with kinesin. J Biol Chem 280, 14723-14732.
111. Chada SR, Hollenbeck PJ (2004) Nerve growth factor signaling regulates motility and docking of axonal mitochondria. CurrBiol 14, 1272-1276.
112. Chada SR, Hollenbeck PJ (2003) Mitochondrial movement and positioning in axons: the role of growth factor signaling. J Exp Biol 206, 1985-1992.
113. Orr AL, Li S, Wang CE, Li H, Wang J, Rong J, Xu X, Mas- troberardino PG, Greenamyre JT, Li XJ (2008) N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci 28, 2783-2792.
114. Weihofen A, Thomas KJ, Ostaszewski BL, Cookson MR, Selkoe DJ (2009) Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 48, 2045-2052.
115. De Vos KJ, Chapman AL, Tennant ME, Manser C, Tudor EL, Lau KF, Brownlees J, Ackerley S, Shaw PJ, McLoughlin DM, Shaw CE, Leigh PN, Miller CC, Grierson AJ (2007) Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 16, 2720-2728.
116. Magrane J, Manfredi G (2009) Mitochondrial function, morphology, and axonal transport in amyotrophic lateral sclerosis. Antioxid Redox Signal 11, 1615-1626.
117. Magrane J, Hervias I, Henning MS, Damiano M, Kawamata H, Manfredi G (2009) Mutant SOD1 in neuronal mitochondria causes toxicity and mitochondrial dynamics abnormalities. Hum Mol Genet 18, 4552-4564.
118. Shi P, Gal J, Kwinter DM, Liu X, Zhu H (2010) Mitochon- drial dysfunction in amyotrophic lateral sclerosis. Biochim BiophysActa 1802, 45-51.
119. Miller KE, Sheetz MP (2004) Axonal mitochondrial transport and potential are correlated. J Cell Sci 117, 2791-2804.
120. Dewil M, dela Cruz VF, Van Den Bosch L, Robberecht W (2007) Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death. Neurobiol Dis 26, 332-341.
121. Morfini G, Pigino G, Opalach K, Serulle Y, Moreira JE, Sugimori M, Llinas RR, Brady ST (2007) 1-Methyl-4- phenylpyridinium affects fast axonal transport by activation of caspase and protein kinase C. Proc Natl Acad Sci U S A 104, 2442-2447.
122. Shibata N, Kawaguchi-Niida M, Yamamoto T, Toi S, Hirano A, Kobayashi M (2008) Effects of the PPARgamma activator pioglitazone on p38 MAP kinase and IkappaBalpha in the spinal cord of a transgenic mouse model of amyotrophic lateral sclerosis. Neuropathology 28, 387-398.
123. Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjorkblom B, Coffey ET, Bagnato C, Han D, Huang CF, Banker G, Pigino G, Brady ST (2009) Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci 12, 864-871.
124. Pigino G, Morfini G, Atagi Y, Deshpande A, Yu C, Jungbauer L, LaDu M, Busciglio J, Brady S (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc Natl Acad Sci USA 106, 5907-5912.
125. Chan DC (2006) Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22, 79-99.
126. Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280,26185-26192.
127. Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schroder JM, Vance JM (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36, 449-451.
128. Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26, 211-215.
129. Smirnova E, Griparic L, Shurland DL, van der Bliek AM (2001) Dynamin-related protein Drp1 is required for mito- chondrial division in mammalian cells. Mol Biol Cell 12, 2245-2256.
130. James DI, Parone PA, Mattenberger Y, Martinou JC (2003) hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem 278, 36373-36379.
131. Sotelo-Silveira JR, Lepanto P, Elizondo MV, Horjales S, Pala- cios F, Martinez Palma L, Marin M, Beckman JS, BarbeitoL (2009) Axonal mitochondrial clusters containing mutant SOD1 in transgenic models of ALS. Antioxid Redox Signal 11, 1535-1545.
132. Magrane J, Manfredi G (2009) Mitochondrial function, morphology, and axonal transport in amyotrophic lateral sclerosis. Antioxid Redox Signal 11, 1615-1626.
133. Wang X, Su B, Fujioka H, Zhu X (2008) Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients. Am J Pathol 173, 470-482.
134. Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci USA 105, 19318-19323.
135. Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 29, 9090-9103.
136. Bossy-Wetzel E, Barsoum MJ, Godzik A, Schwarzenbacher R, Lipton SA (2003) Mitochondrial fission in apoptosis, neu- rodegeneration and aging. Curr Opin Cell Biol 15, 706-716.
137. Karbowski M, Arnoult D, Chen H, Chan DC, Smith CL, Youle RJ (2004) Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochon- drial fusion is blocked during the Bax activation phase of apoptosis. J Cell Biol 164, 493-499.
138. Carriedo SG, Sensi SL, Yin HZ, Weiss JH (2000) AMPA exposures induce mitochondrial Ca(2+) overload and ROS generation in spinal motor neurons in vitro. J Neurosci 20, 240-250.
139. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Lohr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dotsch V, Ney PA, Dikic I (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11, 45-51.
140. Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12, 119-131.
141. Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, Magrane J, Moore DJ, Dawson VL, Grailhe R, Dawson TM, Li C, Tieu K, Przedborski S (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U SA 107, 378-383.
142. Park KH, Vincent I (2008) Presymptomatic biochemical changes in hindlimb muscle of G93A human Cu/Zn super- oxide dismutase 1 transgenic mouse model of amyotrophic lateral sclerosis. Biochim Biophys Acta 1782, 462-468.
143. Gordon T, Ly V, Hegedus J, Tyreman N (2009) Early detection of denervated muscle fibers in hindlimb muscles after sciatic nerve transection in wild type mice and in the G93A mouse model of amyotrophic lateral sclerosis. Neurol Res 31, 28-42.
144. Lemmens R, Van Hoecke A, Hersmus N, Geelen V, D'Hollander I, Thijs V, Van Den Bosch L, Carmeliet P, Rob- berecht W (2007) Overexpression of mutant superoxide dis- mutase 1 causes a motor axonopathy in the zebrafish. Hum Mol Genet 16, 2359-2365.
145. Dupuis L, Gonzalez de Aguilar J-L, Echaniz-Laguna A, Es- chbach J, Rene Fdr, Oudart H, Halter B, Huze C, Schaeffer L, Bouillaud Fdr, Loeffler J-P (2009) Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons. PLoS ONE 4, e5390.
146. Ilieva H, Polymenidou M, Cleveland DW (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 187, 761-772.
147. Pramatarova A, Laganiere J, Roussel J, Brisebois K, Rouleau GA (2001) Neuron-specific expression of mutant superox- ide dismutase 1 in transgenic mice does not lead to motor impairment. J Neurosci 21, 3369-3374.
148. Lino MM, Schneider C, Caroni P (2002) Accumulation of SOD1 mutants in postnatal motoneurons does not cause mo- toneuron pathology or motoneuron disease. J Neurosci 22, 4825-4832.
149. Clement AM, Nguyen MD, Roberts EA, Garcia ML, Boillee S, Rule M, McMahon AP, Doucette W, Siwek D, Ferrante RJ, Brown RH, Jr., Julien JP, Goldstein LS, Cleveland DW (2003) Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302, 113-117.
150. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G, Cleveland DW (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312, 1389-1392.
151. Yamanaka K, Boillee S, Roberts EA, Garcia ML, McAlonis- Downes M, Mikse OR, Cleveland DW, Goldstein LS (2008) Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc Natl Acad Sci USA 105, 7594-7599.
152. Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Ya- mashita H, Gutmann DH, Takahashi R, Misawa H, Cleveland DW (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11, 251-253.
153. Lobsiger CS, Boillee S, McAlonis-Downes M, Khan AM, Feltri ML, Yamanaka K, Cleveland DW (2009) Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc Natl Acad Sci USA 106, 4465-4470.
154. Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (2007) Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 10, 615-622.
155. Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K (2007) Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci 10, 608-614.
156. Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC (2008) Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect ofglial cells carrying an ALS-causing mutation. Cell Stem Cell 3, 637-648.
157. Jaarsma D, Teuling E, Haasdijk ED, De Zeeuw CI, Hoogen- raad CC (2008) Neuron-specific expression of mutant super- oxide dismutase is sufficient to induce amyotrophic lateral sclerosis in transgenic mice. J Neurosci 28, 2075-2088.
158. Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mam- mucari C, Boncompagni S, Belia S, Wannenes F, Nicoletti C, Del Prete Z, Rosenthal N, Molinaro M, Protasi F, Fano G, Sandri M, Musaro A (2008) Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. CellMetab 8, 425436.
159. Wong M, Martin LJ (2010) Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice. Hum Mol Genet 19, 2284-2302.