Mitochondrial dynamic abnormalities in amyotrophic lateral sclerosis

Translational Neurodegeneration

Xinglong Wang¹  Xiongwei Zhu¹  George Perry²  Wenzhang Wang¹  Zhen Jiang¹ 

[1] Department of Pathology, Case Western Reserve University, Cleveland, OH, USA;College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA

关键词: Mitochondrial biogenesis and mitophagy;    Mitochondrial trafficking;    Mitochondrial fission and fusion;    Mitochondrial dynamics;    Mitochondrial dysfunction;    ALS;   

Others  :  1221582
DOI  :  10.1186/s40035-015-0037-x

 received in 2015-05-21, accepted in 2015-07-22,  发布年份 2015

【 摘 要 】

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord. Currently, there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases. Neuronal mitochondria dysfunction is one of the earliest features of ALS. Mitochondria are highly dynamic organelles that undergo continuous fission, fusion, trafficking and turnover, all of which contribute to the maintenance of mitochondrial function. Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS. Here, we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS, and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.

【 授权许可】

   
2015 Jiang et al.

【 参考文献 】

• [1]Gordon PH: Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials. Aging and Dis 2013, 4(5):295-310.
• [2]Leigh PN: Chapter 13 Amyotrophic lateral sclerosis. Handb Clin Neurol 2007, 82:249-78.
• [3]Su B, Wang X, Zheng L, Perry G, Smith MA, Zhu X: Abnormal mitochondrial dynamics and neurodegenerative diseases. Biochim Biophys Acta 2010, 1802(1):135-42.
• [4]Tan W, Pasinelli P, Trotti D: Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis. Biochim Biophys Acta 2014, 1842(8):1295-301.
• [5]Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, et al.: Mitochondrial bioenergetics and structural network organization. J Cell Sci 2007, 120(Pt 5):838-48.
• [6]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.
• [7]Sheng ZH: Mitochondrial trafficking and anchoring in neurons: New insight and implications. J Cell Biol 2014, 204(7):1087-98.
• [8]Kawamata H, Manfredi G: Import, Maturation, and Function of SOD1 and Its Copper Chaperone CCS in the Mitochondrial Intermembrane Space. Antioxid Redox Sign 2010, 13(9):1375-84.
• [9]Mattiazzi M, D’Aurelio M, Gajewski CD, Martushova K, Kiaei M, Beal MF, et al.: Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J Biol Chem 2002, 277(33):29626-33.
• [10]Liu J, Lillo C, Jonsson PA, Vande Velde C, Ward CM, Miller TM, et al.: Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 2004, 43(1):5-17.
• [11]Bergemalm D, Jonsson PA, Graffmo KS, Andersen PM, Brannstrom T, Rehnmark A, et al.: Overloading of stable and exclusion of unstable human superoxide dismutase-1 variants in mitochondria of murine amyotrophic lateral sclerosis models. J Neurosci 2006, 26(16):4147-54.
• [12]Deng HX, Shi Y, Furukawa Y, Zhai H, Fu RG, Liu ED, et al.: Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria. P Natl Acad Sci USA 2006, 103(18):7142-7.
• [13]Israelson A, Arbel N, Da Cruz S, Ilieva H, Yamanaka K, Shoshan-Barmatz V, et al.: Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron 2010, 67(4):575-87.
• [14]Wiedemann FR, Manfredi G, Mawrin C, Beal MF, Schon EA: Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem 2002, 80(4):616-25.
• [15]Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM: Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 1999, 46(5):787-90.
• [16]Genova ML, Pich MM, Bernacchia A, Bianchi C, Biondi A, Bovina C, et al.: The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann N Y Acad Sci 2004, 1011:86-100.
• [17]Adam-Vizi V: Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 2005, 7(9–10):1140-9.
• [18]Pitkanen S, Robinson BH: Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase. J Clin Invest 1996, 98(2):345-51.
• [19]Rizzardini M, Mangolini A, Lupi M, Ubezio P, Bendotti C, Cantoni L: Low levels of ALS-linked Cu/Zn superoxide dismutase increase the production of reactive oxygen species and cause mitochondrial damage and death in motor neuron-like cells. J Neurol Sci 2005, 232(1–2):95-103.
• [20]Shaw PJ, Ince PG, Falkous G, Mantle D: Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol 1995, 38(4):691-5.
• [21]Ikawa M, Okazawa H, Tsujikawa T, Matsunaga A, Yamamura O, Mori T, et al.: Increased oxidative stress is related to disease severity in the ALS motor cortex: A PET study. Neurology 2015, 84(20):2033-9.
• [22]Kihira T, Okamoto K, Yoshida S, Kondo T, Iwai K, Wada S, et al.: Environmental characteristics and oxidative stress of inhabitants and patients with amyotrophic lateral sclerosis in a high-incidence area on the Kii Peninsula, Japan. Int Med 2013, 52(13):1479-86.
• [23]Siklos L, Engelhardt J, Harati Y, Smith RG, Joo F, Appel SH: Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis. Ann Neurol 1996, 39(2):203-16.
• [24]Damiano M, Starkov AA, Petri S, Kipiani K, Kiaei M, Mattiazzi M, et al.: Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J Neurochem 2006, 96(5):1349-61.
• [25]Kim HJ, Magrane J, Starkov AA, Manfredi G: The mitochondrial calcium regulator cyclophilin D is an essential component of oestrogen-mediated neuroprotection in amyotrophic lateral sclerosis. Brain: a J Neurol 2012, 135(Pt 9):2865-74.
• [26]Parone PA, Da Cruz S, Han JS, McAlonis-Downes M, Vetto AP, Lee SK, et al.: Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis. J Neurosci 2013, 33(11):4657-71.
• [27]Tradewell ML, Durham HD: Calpastatin reduces toxicity of SOD1G93A in a culture model of amyotrophic lateral sclerosis. Neuroreport 2010, 21(15):976-9.
• [28]Hirano A, Donnenfeld H, Sasaki S, Nakano I: Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 1984, 43(5):461-70.
• [29]Vande Velde C, McDonald KK, Boukhedimi Y, McAlonis-Downes M, Lobsiger CS, Bel Hadj S, et al.: Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. PLoS One 2011., 6(7) Article ID e22031
• [30]Song W, Song Y, Kincaid B, Bossy B, Bossy-Wetzel E: Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons: neuroprotection by SIRT3 and PGC-1alpha. Neurobiol Dis 2013, 51:72-81.
• [31]Vinsant S, Mansfield C, Jimenez-Moreno R, Del Gaizo MV, Yoshikawa M, Hampton TG, et al.: Characterization of early pathogenesis in the SOD1(G93A) mouse model of ALS: part II, results and discussion. Brain and Behavior 2013, 3(4):431-57.
• [32]Vinsant S, Mansfield C, Jimenez-Moreno R, Del Gaizo MV, Yoshikawa M, Hampton TG, et al.: Characterization of early pathogenesis in the SOD1(G93A) mouse model of ALS: part I, background and methods. Brain and Behavior 2013, 3(4):335-50.
• [33]Magrane J, Cortez C, Gan WB, Manfredi G: Abnormal mitochondrial transport and morphology are common pathological denominators in SOD1 and TDP43 ALS mouse models. Hum Mol Genet 2014, 23(6):1413-24.
• [34]Xu YF, Gendron TF, Zhang YJ, Lin WL, D’Alton S, Sheng H, et al.: Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci 2010, 30(32):10851-9.
• [35]Xu YF, Zhang YJ, Lin WL, Cao X, Stetler C, Dickson DW, et al.: Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice. Mol Neurodegener 2011, 6:73. BioMed Central Full Text
• [36]Wang W, Li L, Lin WL, Dickson DW, Petrucelli L, Zhang T, et al.: The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons. Hum Mol Genet 2013, 22(23):4706-19.
• [37]Chan DC: Mitochondria: dynamic organelles in disease, aging, and development. Cell 2006, 125(7):1241-52.
• [38]Bleazard W, McCaffery JM, King EJ, Bale S, Mozdy A, Tieu Q, et al.: The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1999, 1(5):298-304.
• [39]McBride HM, Neuspiel M, Wasiak S: Mitochondria: more than just a powerhouse. Current Biology : CB 2006, 16(14):R551-60.
• [40]Loson OC, Song Z, Chen H, Chan DC: Fis1, Mff, MiD49 and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell 2013, 24(5):659-67.
• [41]Detmer SA, Chan DC: Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 2007, 8(11):870-9.
• [42]Liu W, Yamashita T, Tian F, Morimoto N, Ikeda Y, Deguchi K, et al.: Mitochondrial fusion and fission proteins expression dynamically change in a murine model of amyotrophic lateral sclerosis. Curr Neurovasc Res 2013, 10(3):222-30.
• [43]Picard M, Shirihai OS, Gentil BJ, Burelle Y: Mitochondrial morphology transitions and functions: implications for retrograde signaling? Am J Physiol Regul Integr Comp Physiol 2013, 304(6):R393-406.
• [44]Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, et al.: Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. Embo J 2008, 27(2):433-46.
• [45]Liu W, Acin-Perez R, Geghman KD, Manfredi G, Lu B, Li C: Pink1 regulates the oxidative phosphorylation machinery via mitochondrial fission. Proc Natl Acad Sci U S A 2011, 108(31):12920-4.
• [46]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.
• [47]Sasaki S, Iwata M: Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2007, 66(1):10-6.
• [48]De Vos KJ, Chapman AL, Tennant ME, Manser C, Tudor EL, Lau KF, et al.: Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 2007, 16(22):2720-8.
• [49]Sotelo-Silveira JR, Lepanto P, Elizondo V, Horjales S, Palacios F, Martinez-Palma L, et al.: Axonal mitochondrial clusters containing mutant SOD1 in transgenic models of ALS. Antioxid Redox Signal 2009, 11(7):1535-45.
• [50]Igaz LM, Kwong LK, Lee EB, Chen-Plotkin A, Swanson E, Unger T, et al.: Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Invest 2011, 121(2):726-38.
• [51]Janssens J, Wils H, Kleinberger G, Joris G, Cuijt I, Ceuterick-de Groote C, et al.: Overexpression of ALS-associated p. M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice. Mol Neurobiol 2013, 48(1):22-35.
• [52]Guo X, Macleod GT, Wellington A, Hu F, Panchumarthi S, Schoenfield M, et al.: The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 2005, 47(3):379-93.
• [53]Kieran D, Hafezparast M, Bohnert S, Dick JR, Martin J, Schiavo G, et al.: A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J Cell Biol 2005, 169(4):561-7.
• [54]Frederick RL, Shaw JM: Moving mitochondria: establishing distribution of an essential organelle. Traffic 2007, 8(12):1668-75.
• [55]Sasaki S, Iwata M: Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotrophic lateral sclerosis. Neurology 1996, 47(2):535-40.
• [56]Silverstein B, Feld S, Kozlowski LT: The availability of low-nicotine cigarettes as a cause of cigarette smoking among teenage females. J Health Soc Behav 1980, 21(4):383-8.
• [57]Schwarz TL: Mitochondrial trafficking in neurons. Cold Spring Harb Perspect Biol 2013, 5:6.
• [58]Zhang F, Wang W, Siedlak SL, Liu Y, Liu J, Jiang K, et al.: Miro1 deficiency in amyotrophic lateral sclerosis. Front Aging Neurosci 2015, 7:100.
• [59]Ligon LA, LaMonte BH, Wallace KE, Weber N, Kalb RG, Holzbaur EL: Mutant superoxide dismutase disrupts cytoplasmic dynein in motor neurons. Neuroreport 2005, 16(6):533-6.
• [60]Wen HL, Lin YT, Ting CH, Lin-Chao S, Li H, Hsieh-Li HM: Stathmin, a microtubule-destabilizing protein, is dysregulated in spinal muscular atrophy. Hum Mol Genet 2010, 19(9):1766-78.
• [61]Lim KL, Ng XH, Grace LG, Yao TP: Mitochondrial dynamics and Parkinson’s disease: focus on parkin. Antioxid Redox Signal 2012, 16(9):935-49.
• [62]Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, et al.: Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999, 98(1):115-24.
• [63]Wang J, Zhang Y, Tang L, Zhang N, Fan D: Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis. Neurosci Lett 2011, 503(3):250-5.
• [64]Stribl C, Samara A, Trumbach D, Peis R, Neumann M, Fuchs H, et al.: Mitochondrial dysfunction and decrease in body weight of a transgenic knock-in mouse model for TDP-43. J Biol Chem 2014, 289(15):10769-84.
• [65]Wong YC, Holzbaur EL: Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A 2014, 111(42):E4439-48.
• [66]Kimura Y, Fukushi J, Hori S, Matsuda N, Okatsu K, Kakiyama Y, et al.: Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system. Genes Cells 2013, 18(12):1131-43.
• [67]Gal J, Strom AL, Kwinter DM, Kilty R, Zhang J, Shi P, et al.: Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism. J Neurochem 2009, 111(4):1062-73.
• [68]Li L, Zhang X, Le W: Altered macroautophagy in the spinal cord of SOD1 mutant mice. Autophagy 2008, 4(3):290-3.
• [69]Zhang XJ, Li LA, Chen S, Yang DH, Wang Y, Zhang X, et al.: Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Autophagy 2011, 7(4):412-25.
• [70]Zhang X, Chen S, Song L, Tang Y, Shen Y, Jia L, et al.: MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy 2014, 10(4):588-602.
• [71]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.
• [72]Zhao T, Huang X, Han L, Wang X, Cheng H, Zhao Y, et al.: Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes. J Biol Chem 2012, 287(28):23615-25.
• [73]Bensimon G, Lacomblez L, Meininger V: A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 1994, 330(9):585-91.
• [74]Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V: Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996, 347(9013):1425-31.
• [75]Cozzolino M, Carri MT: Mitochondrial dysfunction in ALS. Prog Neurobiol 2012, 97(2):54-66.
• [76]Matthews RT, Yang L, Browne S, Baik M, Beal MF: Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A 1998, 95(15):8892-7.
• [77]Bordet T, Buisson B, Michaud M, Drouot C, Galea P, Delaage P, et al.: Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther 2007, 322(2):709-20.
• [78]Martin LJ: Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis. IDrugs: The Invest Drugs J 2010, 13(8):568-80.
• [79]Wang H, Guan Y, Wang X, Smith K, Cormier K, Zhu S, et al.: Nortriptyline delays disease onset in models of chronic neurodegeneration. Eur J Neurosci 2007, 26(3):633-41.
• [80]Keep M, Elmer E, Fong KS, Csiszar K: Intrathecal cyclosporin prolongs survival of late-stage ALS mice. Brain Res 2001, 894(2):327-31.
• [81]Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, et al.: SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 2012, 15(5):675-90.
• [82]Da Cruz S, Parone PA, Lopes VS, Lillo C, McAlonis-Downes M, Lee SK, et al.: Elevated PGC-1alpha activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS. Cell Metab 2012, 15(5):778-86.
• [83]Li Z, Okamoto K, Hayashi Y, Sheng M: The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 2004, 119(6):873-87.
• [84]Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH: Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 2010, 30(12):4232-40.
• [85]Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, et al.: Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 2009, 29(28):9090-103.
• [86]Nguyen TT, Oh SS, Weaver D, Lewandowska A, Maxfield D, Schuler MH, et al.: Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease. Proc Natl Acad Sci U S A 2014, 111(35):E3631-40.
• [87]Shi P, Gal J, Kwinter DM, Liu X, Zhu H: Mitochondrial dysfunction in amyotrophic lateral sclerosis. Biochim Biophys Acta 2010, 1802(1):45-51.
• [88]Archer SL: Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med 2013, 369(23):2236-51.