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PMID: 19081372 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Mitochondria in neuroplasticity and neurological disorders.

Neuron ·Vol. 60 ·No. 5 ·2008-12-10 ·Pages 748-66

Mattson MP, Gleichmann M, Cheng A

Abstract

Mitochondrial electron transport generates the ATP that is essential for the excitability and survival of neurons, and the protein phosphorylation reactions that mediate synaptic signaling and related long-term changes in neuronal structure and function. Mitochondria are highly dynamic organelles that divide, fuse, and move purposefully within axons and dendrites. Major functions of mitochondria in neurons include the regulation of Ca(2+) and redox signaling, developmental and synaptic plasticity, and the arbitration of cell survival and death. The importance of mitochondria in neurons is evident in the neurological phenotypes in rare diseases caused by mutations in mitochondrial genes. Mitochondria-mediated oxidative stress, perturbed Ca(2+) homeostasis, and apoptosis may also contribute to the pathogenesis of prominent neurological diseases including Alzheimer's, Parkinson's, and Huntington's diseases; stroke; amyotrophic lateral sclerosis; and psychiatric disorders. Advances in understanding the molecular and cell biology of mitochondria are leading to novel approaches for the prevention and treatment of neurological disorders.

MeSH Terms
Animals Electron Transport Complex I/metabolism Humans Mitochondria/physiology Mitochondrial Proteins/metabolism Models, Biological Nervous System Diseases/pathology,physiopathology Neuronal Plasticity/physiology
Chemicals
Mitochondrial Proteins Electron Transport Complex I
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mattson Mark P
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov
Gleichmann Marc
Cheng Aiwu
References (204)
204 references, click to expand
  1. Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation.
    Cell. 2008 Jan 11;132(1):137-48 PMID: 18191227
  2. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain.
    J Biol Chem. 2008 Apr 4;283(14):9089-100 PMID: 18245082
  3. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.
    Nat Med. 2003 Aug;9(8):1062-8 PMID: 12858170
  4. The chemistry of peroxynitrite: implications for biological activity.
    Methods Enzymol. 2008;436:49-61 PMID: 18237627
  5. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria.
    Neuron. 2004 Jul 8;43(1):19-30 PMID: 15233914
  6. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.
    Neuromolecular Med. 2006;8(3):389-414 PMID: 16775390
  7. Beta-amyloid precursor protein is a direct cleavage target of HtrA2 serine protease. Implications for the physiological function of HtrA2 in the mitochondria.
    J Biol Chem. 2006 Nov 10;281(45):34277-87 PMID: 16968707
  8. Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase-independent pathway to cell death.
    J Cell Biol. 1997 Oct 6;139(1):205-17 PMID: 9314540
  9. Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants.
    J Neurosci. 2008 Apr 16;28(16):4115-22 PMID: 18417691
  10. The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells.
    J Cell Sci. 2005 Jul 15;118(Pt 14):3049-59 PMID: 15985469
  11. Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism.
    J Neurosci Res. 1999 Sep 15;57(6):830-9 PMID: 10467254
  12. Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons.
    Neurobiol Dis. 2006 May;22(2):388-400 PMID: 16473015
  13. Genetic findings in Parkinson's disease and translation into treatment: a leading role for mitochondria?
    Genes Brain Behav. 2008 Mar;7(2):129-51 PMID: 17680806
  14. Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients.
    Ann Neurol. 1998 Nov;44(5):819-24 PMID: 9818940
  15. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin.
    Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10793-8 PMID: 16818890
  16. Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death.
    J Neurosci. 2006 Jan 4;26(1):41-50 PMID: 16399671
  17. Dynamic role of postsynaptic caspase-3 and BIRC4 in zebra finch song-response habituation.
    Neuron. 2006 Dec 21;52(6):1061-72 PMID: 17178408
  18. Necrotic death of neurons following an excitotoxic insult is prevented by a peptide inhibitor of c-jun N-terminal kinase.
    J Neurochem. 2007 Jul;102(1):65-76 PMID: 17490439
  19. Modifications of microtubule proteins in ALS nerve precede detectable histologic and ultrastructural changes.
    Neurology. 1988 Oct;38(10):1596-600 PMID: 2458547
  20. Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease.
    Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14163-8 PMID: 17715058
  21. Induction of neuronal death by alpha-synuclein.
    Eur J Neurosci. 2000 Aug;12(8):3073-7 PMID: 10971650
  22. alpha-Synuclein locus triplication causes Parkinson's disease.
    Science. 2003 Oct 31;302(5646):841 PMID: 14593171
  23. Evidence for mitochondrial control of neuronal polarity.
    J Neurosci Res. 1999 Apr 1;56(1):8-20 PMID: 10213470
  24. Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations.
    J Cell Biol. 2007 Feb 12;176(4):405-14 PMID: 17296794
  25. Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress.
    Hum Mol Genet. 2005 Jan 1;14(1):71-84 PMID: 15525661
  26. Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis.
    J Neuropathol Exp Neurol. 1988 Nov;47(6):642-53 PMID: 2459315
  27. PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1.
    PLoS Biol. 2007 Jul;5(7):e172 PMID: 17579517
  28. Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats.
    J Neurosci. 2006 Jul 26;26(30):7974-83 PMID: 16870742
  29. NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices.
    J Neurosci. 2003 Apr 15;23(8):3196-208 PMID: 12716927
  30. Putamen mitochondrial energy metabolism is highly correlated to emotional and intellectual impairment in schizophrenics.
    Neuropsychopharmacology. 2000 Mar;22(3):284-92 PMID: 10693156
  31. Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis.
    Cell. 2005 May 20;121(4):579-591 PMID: 15907471
  32. The mitochondrial uncoupler 2,4-dinitrophenol attenuates tissue damage and improves mitochondrial homeostasis following transient focal cerebral ischemia.
    J Neurochem. 2005 Sep;94(6):1676-84 PMID: 16045446
  33. Mitochondrial involvement in post-tetanic potentiation of synaptic transmission.
    Neuron. 1997 Mar;18(3):483-91 PMID: 9115741
  34. Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death.
    J Neurosci. 2007 Feb 14;27(7):1519-28 PMID: 17301160
  35. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase.
    Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14807-12 PMID: 17766438
  36. Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view.
    Biochim Biophys Acta. 2008 Sep;1777(9):1092-7 PMID: 18519024
  37. Ancient invasions: from endosymbionts to organelles.
    Science. 2004 Apr 9;304(5668):253-7 PMID: 15073369
  38. 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes.
    Neuroscience. 1997 Oct;80(3):685-96 PMID: 9276486
  39. Origin and functional consequences of the complex I defect in Parkinson's disease.
    Ann Neurol. 1996 Oct;40(4):663-71 PMID: 8871587
  40. Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria.
    J Biol Chem. 2004 Dec 3;279(49):51654-60 PMID: 15456764
  41. Evidence that caspase-1 is a negative regulator of AMPA receptor-mediated long-term potentiation at hippocampal synapses.
    J Neurochem. 2006 May;97(4):1104-10 PMID: 16573645
  42. Hormesis/preconditioning mechanisms, the nervous system and aging.
    Ageing Res Rev. 2006 May;5(2):165-78 PMID: 16682262
  43. MPTP mechanisms of neurotoxicity and their implications for Parkinson's disease.
    Eur J Pharmacol. 1991 Dec 12;208(4):273-86 PMID: 1815982
  44. Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses.
    Trends Neurosci. 2006 Nov;29(11):632-9 PMID: 17000014
  45. Mitochondria in the aetiology and pathogenesis of Parkinson's disease.
    Lancet Neurol. 2008 Jan;7(1):97-109 PMID: 18093566
  46. The ultrastructure of intramuscular nerves in amyotrophic lateral sclerosis.
    Acta Neuropathol. 1981;55(3):193-8 PMID: 7349578
  47. Increased autophagic degradation of mitochondria in Alzheimer disease.
    Autophagy. 2007 Nov-Dec;3(6):614-5 PMID: 17786024
  48. Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress.
    J Neurosci. 2005 Aug 17;25(33):7567-74 PMID: 16107644
  49. Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis.
    Hum Mol Genet. 2001 Apr 15;10(9):919-26 PMID: 11309365
  50. Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients.
    J Affect Disord. 2003 Sep;76(1-3):55-68 PMID: 12943934
  51. Nortriptyline delays disease onset in models of chronic neurodegeneration.
    Eur J Neurosci. 2007 Aug;26(3):633-41 PMID: 17686041
  52. Evidence that accumulation of ceramides and cholesterol esters mediates oxidative stress-induced death of motor neurons in amyotrophic lateral sclerosis.
    Ann Neurol. 2002 Oct;52(4):448-57 PMID: 12325074
  53. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis.
    Nature. 1999 Aug 26;400(6747):886-91 PMID: 10476969
  54. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking.
    J Neurosci. 2008 Mar 12;28(11):2783-92 PMID: 18337408
  55. The PINK1/Parkin pathway regulates mitochondrial morphology.
    Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1638-43 PMID: 18230723
  56. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits.
    Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17204-9 PMID: 17940007
  57. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction.
    Gene. 2005 Nov 21;361:133-9 PMID: 16203113
  58. Endophilin B1 is required for the maintenance of mitochondrial morphology.
    J Cell Biol. 2004 Sep 27;166(7):1027-39 PMID: 15452144
  59. A hundred years of Alzheimer's disease research.
    Neuron. 2006 Oct 5;52(1):3-13 PMID: 17015223
  60. alpha-synuclein promotes mitochondrial deficit and oxidative stress.
    Am J Pathol. 2000 Aug;157(2):401-10 PMID: 10934145
  61. Pathophysiology of ischaemic stroke: insights from imaging, and implications for therapy and drug discovery.
    Br J Pharmacol. 2008 Mar;153 Suppl 1:S44-54 PMID: 18037922
  62. Mitochondrial abnormalities in Alzheimer's disease.
    J Neurosci. 2001 May 1;21(9):3017-23 PMID: 11312286
  63. Brain-derived neurotrophic factor stimulates energy metabolism in developing cortical neurons.
    J Neurosci. 2003 Sep 10;23(23):8212-20 PMID: 12967982
  64. BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II.
    Eur J Neurosci. 2004 Sep;20(5):1189-96 PMID: 15341590
  65. Coenzyme Q10 improves psychiatric symptoms in adult-onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a case report.
    Aust N Z J Psychiatry. 2000 Dec;34(6):1034-5 PMID: 11127618
  66. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor.
    Science. 2002 Jul 12;297(5579):259-63 PMID: 12114629
  67. Energy metabolism in mammalian brain during development.
    Prog Neurobiol. 2004 Aug;73(6):397-445 PMID: 15313334
  68. Prostate apoptosis response-4 production in synaptic compartments following apoptotic and excitotoxic insults: evidence for a pivotal role in mitochondrial dysfunction and neuronal degeneration.
    J Neurochem. 1999 Jun;72(6):2312-22 PMID: 10349840
  69. Stroke: molecular mechanisms and potential targets for treatment.
    Curr Mol Med. 2003 Jun;3(4):361-72 PMID: 12776991
  70. Amyotrophic lateral sclerosis models and human neuropathology: similarities and differences.
    Acta Neuropathol. 2008 Jan;115(1):97-114 PMID: 18026741
  71. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine.
    Annu Rev Genet. 2005;39:359-407 PMID: 16285865
  72. Mitochondrial fission and fusion dynamics: the long and short of it.
    Cell Death Differ. 2008 Jul;15(7):1147-52 PMID: 18437161
  73. Staging of brain pathology related to sporadic Parkinson's disease.
    Neurobiol Aging. 2003 Mar-Apr;24(2):197-211 PMID: 12498954
  74. Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia.
    Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12005-10 PMID: 16103352
  75. Ca2+, mitochondria and selective motoneuron vulnerability: implications for ALS.
    Trends Neurosci. 2005 Sep;28(9):494-500 PMID: 16026864
  76. Neurotoxic calcium transfer from endoplasmic reticulum to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau.
    J Neurosci. 2005 Apr 20;25(16):4159-68 PMID: 15843619
  77. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid.
    Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61 PMID: 11854529
  78. p53 in neuronal apoptosis.
    Biochem Biophys Res Commun. 2005 Jun 10;331(3):761-77 PMID: 15865932
  79. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice.
    J Biol Chem. 2004 Apr 30;279(18):18614-22 PMID: 14985362
  80. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis.
    Science. 2008 Mar 21;319(5870):1668-72 PMID: 18309045
  81. Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9893-8 PMID: 8790427
  82. Complete dissociation of motor neuron death from motor dysfunction by Bax deletion in a mouse model of ALS.
    J Neurosci. 2006 Aug 23;26(34):8774-86 PMID: 16928866
  83. Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice.
    Mol Cell Biol. 2004 Nov;24(22):9848-62 PMID: 15509788
  84. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases.
    Neuromolecular Med. 2003;4(1-2):21-36 PMID: 14528050
  85. The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.
    Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8 PMID: 15181200
  86. 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease.
    J Neurochem. 2005 Dec;95(6):1521-40 PMID: 16300642
  87. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.
    Neuron. 2000 Jan;25(1):239-52 PMID: 10707987
  88. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis.
    Hum Mol Genet. 2005 Jan 15;14(2):241-53 PMID: 15563509
  89. Mono- and double-mutant mouse models of Parkinson's disease display severe mitochondrial damage.
    Hum Mol Genet. 2007 Oct 15;16(20):2377-93 PMID: 17412759
  90. Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis.
    Clin Neurosci. 1995-1996;3(6):348-59 PMID: 9021256
  91. Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death.
    Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18314-9 PMID: 17116881
  92. Organelle motility and metabolism in axons vs dendrites of cultured hippocampal neurons.
    J Cell Sci. 1996 May;109 ( Pt 5):971-80 PMID: 8743944
  93. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin.
    Nature. 2006 Jun 29;441(7097):1162-6 PMID: 16672981
  94. Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression.
    Hum Mol Genet. 2006 May 1;15(9):1437-49 PMID: 16551656
  95. Differential requirement for caspase 9 in apoptotic pathways in vivo.
    Cell. 1998 Aug 7;94(3):339-52 PMID: 9708736
  96. Axonal mitochondrial transport and potential are correlated.
    J Cell Sci. 2004 Jun 1;117(Pt 13):2791-804 PMID: 15150321
  97. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.
    Hum Mol Genet. 2005 Jul 15;14(14):2063-73 PMID: 15944198
  98. Caspase-dependent and -independent neuronal death: two distinct pathways to neuronal injury.
    Neuroscientist. 2005 Feb;11(1):50-62 PMID: 15632278
  99. Participation of the mitochondrial genome in the differentiation of neuroblastoma cells.
    In Vitro Cell Dev Biol. 1992 Nov-Dec;28A(11-12):763-72 PMID: 1483966
  100. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration.
    Cell Metab. 2006 Nov;4(5):349-62 PMID: 17055784
  101. Bioenergetic approaches for neuroprotection in Parkinson's disease.
    Ann Neurol. 2003;53 Suppl 3:S39-47; discussion S47-8 PMID: 12666097
  102. Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled.
    J Neurosci. 2006 May 10;26(19):5256-64 PMID: 16687518
  103. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis.
    Ann Neurol. 1997 Oct;42(4):644-54 PMID: 9382477
  104. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death.
    Hum Mol Genet. 2003 Mar 1;12(5):517-26 PMID: 12588799
  105. Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells.
    J Biol Chem. 2006 Dec 8;281(49):37391-403 PMID: 17035241
  106. Intrathecal cyclosporin prolongs survival of late-stage ALS mice.
    Brain Res. 2001 Mar 16;894(2):327-31 PMID: 11251210
  107. Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice.
    J Neurosci. 2006 May 10;26(19):5167-79 PMID: 16687508
  108. Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice--a model of familial Parkinson's disease.
    Neurobiol Dis. 2005 Apr;18(3):492-8 PMID: 15755676
  109. Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria.
    Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):4022-7 PMID: 18296640
  110. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines.
    Nat Neurosci. 2002 Aug;5(8):731-6 PMID: 12089530
  111. Apoptosis in amyotrophic lateral sclerosis: a review of the evidence.
    Neuropathol Appl Neurobiol. 2001 Aug;27(4):257-74 PMID: 11532157
  112. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues.
    Mol Cell. 2000 Dec;6(6):1389-99 PMID: 11163212
  113. Dynamic distribution of endoplasmic reticulum in hippocampal neuron dendritic spines.
    Eur J Neurosci. 2005 Oct;22(7):1793-8 PMID: 16197520
  114. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin.
    J Neurosci. 2007 Nov 7;27(45):12413-8 PMID: 17989306
  115. Calpain activation and not oxidative damage mediates L-2-chloropropionic acid-induced cerebellar granule cell necrosis.
    Toxicol Appl Pharmacol. 1997 Feb;142(2):248-55 PMID: 9070346
  116. Apaf1 is required for mitochondrial pathways of apoptosis and brain development.
    Cell. 1998 Sep 18;94(6):739-50 PMID: 9753321
  117. Dependence of permeability transition pore opening and cytochrome C release from mitochondria on mitochondria energetic status.
    Mol Cell Biochem. 2001 Aug;224(1-2):1-7 PMID: 11693186
  118. Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brain.
    Dev Biol. 2003 Jun 15;258(2):319-33 PMID: 12798291
  119. A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin.
    Ageing Res Rev. 2004 Nov;3(4):445-64 PMID: 15541711
  120. Mitochondrial dysfunction as the molecular basis of bipolar disorder: therapeutic implications.
    CNS Drugs. 2007;21(1):1-11 PMID: 17190525
  121. Review of the literature on major mental disorders in adult patients with mitochondrial diseases.
    Psychosomatics. 2006 Jan-Feb;47(1):1-7 PMID: 16384802
  122. Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials.
    Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13860-5 PMID: 16945901
  123. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease.
    Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2070-5 PMID: 14970312
  124. Detrimental deletions: mitochondria, aging and Parkinson's disease.
    Bioessays. 2006 Oct;28(10):963-7 PMID: 16998822
  125. Transient spine expansion and learning-induced plasticity in layer 1 primary motor cortex.
    J Neurosci. 2008 May 28;28(22):5686-90 PMID: 18509029
  126. Therapeutic potential of excitatory amino acid antagonists: channel blockers and 2,3-benzodiazepines.
    Trends Pharmacol Sci. 1993 Sep;14(9):325-31 PMID: 7504360
  127. Bax, reactive oxygen, and cytochrome c release in neuronal apoptosis.
    Antioxid Redox Signal. 2003 Oct;5(5):589-96 PMID: 14580315
  128. Hippocampal hypometabolism predicts cognitive decline from normal aging.
    Neurobiol Aging. 2008 May;29(5):676-92 PMID: 17222480
  129. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.
    Nature. 1996 Nov 28;384(6607):368-72 PMID: 8934524
  130. Cytosolic Ca2+ changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na+-dependent Ca2+ release from mitochondria.
    J Neurosci. 1999 May 1;19(9):3307-15 PMID: 10212290
  131. ALS: a disease of motor neurons and their nonneuronal neighbors.
    Neuron. 2006 Oct 5;52(1):39-59 PMID: 17015226
  132. Structural basis of mitochondrial tethering by mitofusin complexes.
    Science. 2004 Aug 6;305(5685):858-62 PMID: 15297672
  133. Direct cleavage of AMPA receptor subunit GluR1 and suppression of AMPA currents by caspase-3: implications for synaptic plasticity and excitotoxic neuronal death.
    Neuromolecular Med. 2002;1(1):69-79 PMID: 12025817
  134. Protective effects of NIM811 in transient focal cerebral ischemia suggest involvement of the mitochondrial permeability transition.
    J Neurotrauma. 2007 May;24(5):895-908 PMID: 17518543
  135. Mitochondrial porin required for ischemia-induced mitochondrial dysfunction and neuronal damage.
    Neuroscience. 2000;97(2):363-9 PMID: 10799768
  136. Apoptosis-inducing factor substitutes for caspase executioners in NMDA-triggered excitotoxic neuronal death.
    J Neurosci. 2004 Dec 1;24(48):10963-73 PMID: 15574746
  137. BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15318-23 PMID: 11742085
  138. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin.
    Nature. 1997 Aug 28;388(6645):882-7 PMID: 9278050
  139. Genetics of familial and sporadic amyotrophic lateral sclerosis.
    Biochim Biophys Acta. 2006 Nov-Dec;1762(11-12):956-72 PMID: 16503123
  140. Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA-induced apoptosis in YAC128 model of Huntington's disease.
    J Neurosci. 2007 Dec 12;27(50):13614-23 PMID: 18077673
  141. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4078-83 PMID: 12642658
  142. Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans.
    J Biol Chem. 2005 Dec 30;280(52):42655-42668 PMID: 16239214
  143. Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein.
    Neuron. 2002 Dec 19;36(6):1063-77 PMID: 12495622
  144. Caspase-mediated degradation of AMPA receptor subunits: a mechanism for preventing excitotoxic necrosis and ensuring apoptosis.
    J Neurosci. 2000 May 15;20(10):3641-9 PMID: 10804206
  145. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease.
    Neuron. 2005 Jul 7;47(1):29-41 PMID: 15996546
  146. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD.
    Nature. 1998 Jan 1;391(6662):43-50 PMID: 9422506
  147. Changes in mitochondrial function resulting from synaptic activity in the rat hippocampal slice.
    J Neurosci. 1998 Jun 15;18(12):4570-87 PMID: 9614233
  148. Organization of mitochondria in olfactory bulb granule cell dendritic spines.
    Synapse. 1991 Jun;8(2):107-18 PMID: 1715612
  149. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration.
    Cell. 2006 Oct 6;127(1):59-69 PMID: 17018277
  150. Novel p53 inactivators with neuroprotective action: syntheses and pharmacological evaluation of 2-imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-imino-2,3,4,5,6,7-hexahydrobenzoxazole derivatives.
    J Med Chem. 2002 Nov 7;45(23):5090-7 PMID: 12408720
  151. Mitochondrial regulation of synaptic plasticity in the hippocampus.
    J Biol Chem. 2003 May 16;278(20):17727-34 PMID: 12604600
  152. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses.
    Cell. 2004 Dec 17;119(6):873-87 PMID: 15607982
  153. 4-Hydroxynonenal, a product of lipid peroxidation, damages cholinergic neurons and impairs visuospatial memory in rats.
    J Neuropathol Exp Neurol. 1998 Mar;57(3):257-67 PMID: 9600218
  154. Tiagabine is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's disease.
    Neurobiol Dis. 2008 Jun;30(3):293-302 PMID: 18395459
  155. A century of Alzheimer's disease.
    Science. 2006 Nov 3;314(5800):777-81 PMID: 17082447
  156. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction.
    J Neurosci. 1998 Jan 15;18(2):687-97 PMID: 9425011
  157. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients.
    Neurobiol Aging. 2000 May-Jun;21(3):455-62 PMID: 10858595
  158. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease.
    Science. 2004 Apr 16;304(5669):448-52 PMID: 15087549
  159. Evidence for synaptic apoptosis.
    Exp Neurol. 1998 Sep;153(1):35-48 PMID: 9743565
  160. Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons.
    Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4892-7 PMID: 18347331
  161. Strain-dependent neurodevelopmental abnormalities in caspase-3-deficient mice.
    J Neuropathol Exp Neurol. 2002 Aug;61(8):673-7 PMID: 12152782
  162. Paroxetine retards disease onset and progression in Huntingtin mutant mice.
    Ann Neurol. 2004 Apr;55(4):590-4 PMID: 15048901
  163. Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release.
    Hum Mol Genet. 2004 Jul 15;13(14):1407-20 PMID: 15163634
  164. 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. 1999 Nov;160(1):28-39 PMID: 10630188
  165. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice.
    J Neurosci. 2003 Oct 15;23(28):9418-27 PMID: 14561870
  166. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.
    Nat Med. 1999 Mar;5(3):347-50 PMID: 10086395
  167. Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis.
    EMBO J. 2006 Sep 6;25(17):4061-73 PMID: 16917506
  168. Apoptosis and necrosis in health and disease: role of mitochondria.
    Int Rev Cytol. 2003;224:29-55 PMID: 12722948
  169. Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1.
    J Neurosci. 1998 May 1;18(9):3241-50 PMID: 9547233
  170. Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
    Trends Neurosci. 2008 Sep;31(9):454-63 PMID: 18675468
  171. Depressive disorder due to mitochondrial transfer RNALeu(UUR) mutation.
    Biol Psychiatry. 1997 Jun 1;41(11):1137-9 PMID: 9146825
  172. Caspase activity is essential for long-term potentiation.
    J Neurosci Res. 2003 Sep 15;73(6):853-64 PMID: 12949912
  173. Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
    J Neurosci. 2003 Jun 1;23(11):4499-508 PMID: 12805290
  174. Response of mitochondrial traffic to axon determination and differential branch growth.
    J Neurosci. 2003 Sep 17;23(24):8618-24 PMID: 13679431
  175. Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells.
    Mol Cell Biol. 2007 Jun;27(12):4293-305 PMID: 17438128
  176. Paradigm lost: milton connects kinesin heavy chain to miro on mitochondria.
    J Cell Biol. 2006 May 22;173(4):459-61 PMID: 16717123
  177. Interactions between mitochondrial bioenergetics and cytoplasmic calcium in cultured cerebellar granule cells.
    Cell Calcium. 2003 Oct-Nov;34(4-5):407-24 PMID: 12909085
  178. Mitochondrial Ca2+ as a key regulator of cell life and death.
    Cell Death Differ. 2007 Jul;14(7):1267-74 PMID: 17431419
  179. Activation of mitochondrial ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of Bax translocation and cytochrome c release.
    J Cereb Blood Flow Metab. 2002 Apr;22(4):431-43 PMID: 11919514
  180. Huntington's disease.
    Lancet. 2007 Jan 20;369(9557):218-28 PMID: 17240289
  181. Ceramide-induced neuronal apoptosis is associated with dephosphorylation of Akt, BAD, FKHR, GSK-3beta, and induction of the mitochondrial-dependent intrinsic caspase pathway.
    Mol Cell Neurosci. 2003 Mar;22(3):365-82 PMID: 12691738
  182. Nerve growth factor signaling regulates motility and docking of axonal mitochondria.
    Curr Biol. 2004 Jul 27;14(14):1272-6 PMID: 15268858
  183. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?
    Neurobiol Learn Mem. 2008 Mar;89(3):312-23 PMID: 17942328
  184. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery.
    Proc Natl Acad Sci U S A. 2008 May 13;105(19):7070-5 PMID: 18443288
  185. Differences in mitochondrial movement and morphology in young and mature primary cortical neurons in culture.
    Neuroscience. 2006 Aug 25;141(2):727-736 PMID: 16797853
  186. Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death.
    J Neurosci. 1998 Jul 15;18(14):5151-9 PMID: 9651198
  187. Mitochondrial dynamics and division in budding yeast.
    Trends Cell Biol. 2002 Apr;12(4):178-84 PMID: 11978537
  188. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions.
    Neuron. 2005 Aug 4;47(3):365-78 PMID: 16055061
  189. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons.
    EMBO J. 2006 Aug 23;25(16):3900-11 PMID: 16874299
  190. Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology.
    Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6072-7 PMID: 17389365
  191. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review.
    Acta Psychiatr Scand. 2000 Jan;101(1):11-20 PMID: 10674946
  192. Mitochondrial involvement in psychiatric disorders.
    Ann Med. 2008;40(4):281-95 PMID: 18428021
  193. Differential effects of mitochondrial heat shock protein 60 and related molecular chaperones to prevent intracellular beta-amyloid-induced inhibition of complex IV and limit apoptosis.
    J Biol Chem. 2006 Oct 6;281(40):29468-78 PMID: 16887805
  194. Superoxide flashes in single mitochondria.
    Cell. 2008 Jul 25;134(2):279-90 PMID: 18662543
  195. Cybrids in Alzheimer's disease: a cellular model of the disease?
    Neurology. 1997 Oct;49(4):918-25 PMID: 9339668
  196. The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown.
    Ann N Y Acad Sci. 2008 Mar;1123:197-212 PMID: 18375592
  197. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content.
    Hum Mol Genet. 2007 Nov 15;16(22):2720-2728 PMID: 17725983
  198. Moving mitochondria: establishing distribution of an essential organelle.
    Traffic. 2007 Dec;8(12):1668-1675 PMID: 17944806
  199. The axonal transport of mitochondria.
    J Cell Sci. 2005 Dec 1;118(Pt 23):5411-9 PMID: 16306220
  200. Mutant huntingtin expression induces mitochondrial calcium handling defects in clonal striatal cells: functional consequences.
    J Biol Chem. 2006 Nov 17;281(46):34785-95 PMID: 16973623
  201. Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses.
    J Neurosci. 2002 Jul 15;22(14):5840-7 PMID: 12122046
  202. The apoptosome: signalling platform of cell death.
    Nat Rev Mol Cell Biol. 2007 May;8(5):405-13 PMID: 17377525
  203. Diagnostic criteria and outcome measurement of amyotrophic lateral sclerosis.
    Adv Neurol. 2002;88:53-62 PMID: 11908236
  204. Pathways towards and away from Alzheimer's disease.
    Nature. 2004 Aug 5;430(7000):631-9 PMID: 15295589
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2008.10.010
Email
mattsonm@grc.nia.nih.gov
Published
2008-12-10
Pages
748-66
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2692277
Subset
IM
Grants
Intramural NIH HHS · Z01 AG000317-07 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2008.10.010 PMC Full Text View journal details
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