title: Mitochondrial functional alterations in relation to pathophysiology of Huntington's disease.
abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease which is characterized by psychiatric symptoms, involuntary choreiform movements and dementia with maximum degeneration occurring in striatum and cerebral cortex. Several studies implicate mitochondrial dysfunction to the selective neurodegeneration happening in this disorder. Calcium buffering imbalance and oxidative stress in the mitochondria, critically impaired movement across axons and abnormal fission or fusion of this organelle in the cells are some of the salient features that results in the loss of mitochondrial electron transport chain (ETC) complex function in HD. Although several models involving mutant huntingtin, excitotoxins and mitochondrial complex-II inhibitors have been used to explore the disease, it is not clear how disturbances in mitochondrial functioning is associated with such selective neurodegeneration, or in the expression of huntingtonian phenotypes in animals or man. We have carefully assessed various mitochondrial abnormalities observed in human patient samples, postmortem HD brains, cellular, vertebrate and invertebrate models of the disease, to conclude that ETC dysfunction is an integral part of the disease and justify a causal role of mitochondrial ETC dysfunction for the genesis of this disorder.
authors.affiliation: Division of Cell Biology & Physiology, Laboratory of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology (CSIR), 4, Raja S. C. Mullick Road, Kolkata, 700 032, India.
authors.forename: Mritunjay
authors.initials: M
authors.lastname: Pandey
authors.forename: Kochupurackal P
authors.initials: KP
authors.lastname: Mohanakumar
authors.forename: Rajamma
authors.initials: R
authors.lastname: Usha
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D045222:Electron Transport Chain Complex Proteins; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D009410:Nerve Degeneration
chemical_list: D045222:Electron Transport Chain Complex Proteins
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12218-23
references.pmid: 16103364
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7105-9
references.pmid: 7624378
references.citation: Hum Mol Genet. 2004 Jul 15;13(14):1407-20
references.pmid: 15163634
references.citation: Cell. 1993 Mar 26;72(6):971-83
references.pmid: 8458085
references.citation: Biochem Biophys Res Commun. 2006 Mar 31;342(1):184-90
references.pmid: 16472774
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11035-40
references.pmid: 12958210
references.citation: Neuromolecular Med. 2002;1(3):183-95
references.pmid: 12095160
references.citation: Hum Mol Genet. 2007 Apr 1;16(7):783-97
references.pmid: 17356014
references.citation: Exp Neurol. 2001 Jun;169(2):340-50
references.pmid: 11358447
references.citation: Nat Med. 1999 Oct;5(10):1194-8
references.pmid: 10502825
references.citation: Hum Mol Genet. 1999 Mar;8(3):397-407
references.pmid: 9949199
references.citation: Neurobiol Dis. 2006 May;22(2):388-400
references.pmid: 16473015
references.citation: Mech Ageing Dev. 2006 Feb;127(2):217-20
references.pmid: 16289240
references.citation: Neurochem Res. 2006 Sep;31(9):1103-9
references.pmid: 16944322
references.citation: Neurochem Int. 2006 Jan;48(2):93-9
references.pmid: 16290265
references.citation: J Neurosci. 2004 Jan 7;24(1):269-81
references.pmid: 14715959
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2945-9
references.pmid: 17299049
references.citation: J Cell Physiol. 2006 Feb;206(2):347-53
references.pmid: 16110491
references.citation: J Biol Chem. 2004 May 7;279(19):20211-20
references.pmid: 14981075
references.citation: Biochem Biophys Res Commun. 2007 Jul 27;359(2):335-40
references.pmid: 17543886
references.citation: J Neurochem. 1992 Nov;59(5):1609-23
references.pmid: 1402908
references.citation: Hum Mol Genet. 2009 Aug 15;18(16):3048-65
references.pmid: 19460884
references.citation: J Neurosci. 2006 Oct 25;26(43):11174-86
references.pmid: 17065457
references.citation: FASEB J. 1999 Jun;13(9):1099-106
references.pmid: 10336893
references.citation: Neuron. 2003 Sep 25;40(1):25-40
references.pmid: 14527431
references.citation: J Neurosci Res. 2007 Jun;85(8):1774-88
references.pmid: 17455294
references.citation: J Biol Chem. 2000 May 12;275(19):14064-9
references.pmid: 10799480
references.citation: Neurobiol Aging. 1994 Mar-Apr;15(2):275-6
references.pmid: 7838311
references.citation: Brain Res Rev. 2009 Jun;61(1):33-48
references.pmid: 19394359
references.citation: Am J Hum Genet. 1996 Jul;59(1):16-22
references.pmid: 8659522
references.citation: J Cell Sci. 2009 Mar 15;122(Pt 6):875-85
references.pmid: 19240112
references.citation: Hum Mol Genet. 2007 Jan 1;16(1):61-77
references.pmid: 17135277
references.citation: Mol Cell Biol. 2004 Sep;24(18):8195-209
references.pmid: 15340079
references.citation: J Neurosci. 2008 Mar 12;28(11):2783-92
references.pmid: 18337408
references.citation: Eur J Neurosci. 2006 Jan;23(1):11-20
references.pmid: 16420411
references.citation: Exp Neurol. 2010 Apr;222(2):243-55
references.pmid: 20079354
references.citation: Neurology. 2006 Jan 24;66(2):250-2
references.pmid: 16434666
references.citation: Exp Neurol. 1995 Jun;133(2):265-72
references.pmid: 7649231
references.citation: Mol Neurodegener. 2009 Jun 17;4:26
references.pmid: 19534794
references.citation: Cell. 1996 Nov 1;87(3):493-506
references.pmid: 8898202
references.citation: J Neurosci. 1993 Oct;13(10):4181-92
references.pmid: 7692009
references.citation: J Neural Transm Suppl. 2004;(68):111-6
references.pmid: 15354396
references.citation: Neurosci Lett. 1999 Sep 3;272(1):53-6
references.pmid: 10507541
references.citation: Neurochem Res. 2007 Jul;32(7):1238-47
references.pmid: 17401660
references.citation: Glia. 2009 Nov 1;57(14):1480-91
references.pmid: 19306371
references.citation: J Neurosci. 1998 Dec 1;18(23):10116-27
references.pmid: 9822765
references.citation: Arch Neurol. 2001 Mar;58(3):365-70
references.pmid: 11255439
references.citation: Nature. 1986 May 8-14;321(6066):168-71
references.pmid: 2422561
references.citation: J Neurosci. 2008 Sep 17;28(38):9473-85
references.pmid: 18799679
references.citation: J Neurochem. 2007 Apr;101(1):241-9
references.pmid: 17394466
references.citation: Ann Neurol. 1997 Feb;41(2):160-5
references.pmid: 9029064
references.citation: J Biol Chem. 2001 May 4;276(18):14545-8
references.pmid: 11278258
references.citation: J Biol Chem. 2005 Sep 2;280(35):30773-82
references.pmid: 15983033
references.citation: Hum Mol Genet. 1998 Sep;7(9):1355-61
references.pmid: 9700187
references.citation: Cell Metab. 2006 Nov;4(5):349-62
references.pmid: 17055784
references.citation: Neurochem Int. 2010 Jan;56(2):357-62
references.pmid: 19931335
references.citation: Mol Biol Cell. 2006 Apr;17(4):1652-63
references.pmid: 16452635
references.citation: Nature. 2008 Jun 12;453(7197):921-4
references.pmid: 18488016
references.citation: Nat Neurosci. 2002 Aug;5(8):731-6
references.pmid: 12089530
references.citation: J Biol Chem. 2005 Dec 9;280(49):40398-401
references.pmid: 16207717
references.citation: Cell Death Differ. 2009 Jun;16(6):899-909
references.pmid: 19300456
references.citation: Mov Disord. 2007 Sep 15;22(12):1715-21
references.pmid: 17557337
references.citation: Nature. 1976 Oct 7;263(5577):517-9
references.pmid: 9592
references.citation: Hum Mol Genet. 2009 Feb 15;18(4):737-52
references.pmid: 19039036
references.citation: Brain Res Brain Res Rev. 1995 Jan;20(1):91-127
references.pmid: 7711769
references.citation: J Biol Chem. 2009 Feb 20;284(8):5010-20
references.pmid: 19106091
references.citation: Neurology. 1990 Aug;40(8):1231-4
references.pmid: 2143271
references.citation: J Neurochem. 2001 Dec;79(6):1246-9
references.pmid: 11752065
references.citation: Nat Genet. 1998 Oct;20(2):198-202
references.pmid: 9771716
references.citation: Free Radic Biol Med. 2008 Sep 1;45(5):667-78
references.pmid: 18588971
references.citation: Neuron. 1999 May;23(1):181-92
references.pmid: 10402204
references.citation: Ann Neurol. 1997 May;41(5):646-53
references.pmid: 9153527
references.citation: J Neurosci. 2001 Dec 1;21(23):9112-23
references.pmid: 11717344
references.citation: Ann Neurol. 1996 Mar;39(3):385-9
references.pmid: 8602759
references.citation: Exp Neurol. 1998 Apr;150(2):213-22
references.pmid: 9527890
references.citation: J Neurosci. 2007 Dec 12;27(50):13614-23
references.pmid: 18077673
references.citation: Ann Neurol. 1998 Mar;43(3):397-400
references.pmid: 9506560
references.citation: J Neuropathol Exp Neurol. 1985 Nov;44(6):559-77
references.pmid: 2932539
references.citation: Cell. 2006 Oct 6;127(1):59-69
references.pmid: 17018277
references.citation: Endocr Rev. 2003 Feb;24(1):78-90
references.pmid: 12588810
references.citation: J Neurochem. 2004 Mar;88(5):1220-8
references.pmid: 15009678
references.citation: J Neurosci. 2003 Jun 15;23(12):5020-30
references.pmid: 12832525
references.citation: Nat Genet. 1993 Nov;5(3):259-65
references.pmid: 8275091
references.citation: Am J Physiol Cell Physiol. 2007 Jan;292(1):C157-63
references.pmid: 16870828
references.citation: Mol Neurodegener. 2008 Dec 29;3:21
references.pmid: 19114014
references.citation: Ann Neurol. 1999 Jan;45(1):25-32
references.pmid: 9894873
references.citation: Hum Mol Genet. 2001 May 1;10(10):1049-59
references.pmid: 11331615
references.citation: DNA Repair (Amst). 2009 Jan 1;8(1):126-36
references.pmid: 18935984
references.citation: J Neurochem. 2008 Jan;104(2):420-34
references.pmid: 17953654
references.citation: Hum Mol Genet. 1999 May;8(5):763-74
references.pmid: 10196365
references.citation: J Neurochem. 2002 Feb;80(3):466-76
references.pmid: 11905993
references.citation: Cell Calcium. 2003 Oct-Nov;34(4-5):399-405
references.pmid: 12909084
references.citation: Neurochem Int. 2009 Nov;55(6):431-7
references.pmid: 19410615
references.citation: J Cell Biol. 2005 Dec 19;171(6):1001-12
references.pmid: 16365166
references.citation: Hum Mol Genet. 2003 Mar 1;12(5):497-508
references.pmid: 12588797
references.citation: J Neurol. 2007 Dec;254(12):1676-83
references.pmid: 17990062
references.citation: Biochim Biophys Acta. 2010 Jan;1802(1):62-5
references.pmid: 19591925
references.citation: J Neurosci. 2006 Mar 8;26(10):2830-8
references.pmid: 16525063
references.citation: J Neurosci. 2002 Jun 15;22(12):4842-9
references.pmid: 12077181
references.citation: Biochim Biophys Acta. 2009 Jan;1792(1):68-74
references.pmid: 18973805
references.citation: J Cell Biochem. 2006 May 1;98(1):93-101
references.pmid: 16365893
references.citation: J Neurosci Res. 1999 Nov 15;58(4):515-32
references.pmid: 10533044
references.citation: Biochem Biophys Res Commun. 1999 Aug 11;261(3):701-4
references.pmid: 10441489
references.citation: Hum Mol Genet. 2008 May 15;17(10):1446-56
references.pmid: 18267960
references.citation: J Biol Chem. 2007 Nov 9;282(45):32821-6
references.pmid: 17785462
references.citation: J Biol Chem. 2003 Oct 31;278(44):43245-53
references.pmid: 12917435
references.citation: J Biol Chem. 2008 Feb 29;283(9):5780-9
references.pmid: 18156184
references.citation: J Biol Chem. 2006 Nov 17;281(46):34785-95
references.pmid: 16973623
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1589-94
references.pmid: 10677504
references.citation: J Neurochem. 1985 Jun;44(6):1948-50
references.pmid: 2985766