Inhibition of mitochondrial protein import by mutant huntingtin

Nature Neuroscience

Volumn 17, Issue 6, 2014, Pages 822-831

  Yano, Hiroko ^a,b   Baranov, Sergei V ^a   Baranova, Oxana V ^a   Kim, Jinho ^a   Pan, Yanchun ^b   Yablonska, Svitlana ^a   Carlisle, Diane L ^a   Ferrante, Robert J ^a   Kim, Albert H ^b   Friedlander, Robert M ^a,c  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HUNTINGTIN; MITOCHONDRIAL PROTEIN; MUTANT HUNTINGTIN; TIM23 MITOCHONDRIAL PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN MITOCHONDRION; BRAIN SYNAPTOSOME; CAG REPEAT; CAUDATE NUCLEUS; CELL POPULATION; CELL SURVIVAL; CELLULAR DISTRIBUTION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DISEASE SEVERITY; EMBRYONIC STEM CELL; HUNTINGTON CHOREA; IMMUNOBLOTTING; IMMUNOFLUORESCENCE MICROSCOPY; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; LIVER MITOCHONDRION; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SYNAPTIC TRANSMISSION;

AGED; ANIMALS; CELLS, CULTURED; FEMALE; HEK293 CELLS; HUMANS; HUNTINGTON DISEASE; MALE; MICE; MICE, INBRED CBA; MICE, TRANSGENIC; MIDDLE AGED; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MUTATION; NERVE TISSUE PROTEINS; PROTEIN TRANSPORT;

EID: 84901592715     PISSN: 10976256     EISSN: 15461726     Source Type: Journal    
DOI: 10.1038/nn.3721     Document Type: Article

References (54)

1. Hersch, S.M., Rosas, H.R. & Ferrante, R.J. Neuropathology and pathophysiology of Huntington's disease. in Movement Disorders 3rd edn. (eds. Watts, R.L., Standaert, D.G. & Obeso, J.A.) 683 (McGraw-Hill, New York, 2012).
2. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971-983 (1993).
3. Damiano, M., Galvan, L., Deglon, N. & Brouillet, E. Mitochondria in Huntington's disease. Biochim. Biophys. Acta 1802, 52-61 (2010).
4. Costa, V. & Scorrano, L. Shaping the role of mitochondria in the pathogenesis of Huntington's disease. EMBO J. 31, 1853-1864 (2012).
5. Reddy, P.H. & Shirendeb, U.P. Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease. Biochim. Biophys. Acta 1822, 101-110 (2012).
6. Bates, G. Huntingtin aggregation and toxicity in Huntington's disease. Lancet 361, 1642-1644 (2003).
7. Li, H., Li, S.H., Johnston, H., Shelbourne, P.F. & Li, X.J. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet. 25, 385-389 (2000).
8. Di Figlia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990-1993 (1997).
9. Orr, A.L. et al. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J. Neurosci. 28, 2783-2792 (2008).
10. Yu, Z.X. et al. Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease. J. Neurosci. 23, 2193-2202 (2003).
11. Song, W. et al. Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat. Med. 17, 377-382 (2011).
12. Chacinska, A., Koehler, C.M., Milenkovic, D., Lithgow, T. & Pfanner, N. Importing mitochondrial proteins: machineries and mechanisms. Cell 138, 628-644 (2009).
13. Baker, M.J., Frazier, A.E., Gulbis, J.M. & Ryan, M.T. Mitochondrial protein-import machinery: correlating structure with function. Trends Cell Biol. 17, 456-464 (2007).
14. MacKenzie, J.A. & Payne, R.M. Mitochondrial protein import and human health and disease. Biochim. Biophys. Acta 1772, 509-523 (2007).
15. Li, H., Li, S.H., Yu, Z.X., Shelbourne, P. & Li, X.J. Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease mice. J. Neurosci. 21, 8473-8481 (2001).
16. Panov, A.V. et al. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci. 5, 731-736 (2002).
17. Rockabrand, E. et al. The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum. Mol. Genet. 16, 61-77 (2007).
18. Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506 (1996).
19. Browne, S.E. et al. Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann. Neurol. 41, 646-653 (1997).
20. Gu, M. et al. Mitochondrial defect in Huntington's disease caudate nucleus. Ann. Neurol. 39, 385-389 (1996).
21. Browne, S.E. & Beal, M.F. The energetics of Huntington's disease. Neurochem. Res. 29, 531-546 (2004).
22. Ona, V.O. et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 399, 263-267 (1999).
23. Wang, X. et al. Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington's disease. Proc. Natl. Acad. Sci. USA 100, 10483-10487 (2003).
24. Choo, Y.S., Johnson, G.V., MacDonald, M., Detloff, P.J. & Lesort, M. Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum. Mol. Genet. 13, 1407-1420 (2004).
25. Kim, J. et al. Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease. Hum. Mol. Genet. 19, 3919-3935 (2010).
26. Reddy, P.H. et al. Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim. Biophys. Acta 1822, 639-649 (2012).
27. Costa, V. et al. Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli. EMBO Mol. Med. 2, 490-503 (2010).
28. Gines, S. et al. Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum. Mol. Genet. 12, 497-508 (2003).
29. Mochel, F. et al. Early alterations of brain cellular energy homeostasis in Huntington disease models. J. Biol. Chem. 287, 1361-1370 (2012).
30. Mochel, F. & Haller, R.G. Energy deficit in Huntington disease: why it matters. J. Clin. Invest. 121, 493-499 (2011).
31. Acevedo-Torres, K. et al. Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease. DNA Repair (Amst.) 8, 126-136 (2009).
32. Shirendeb, U.P. et al. Mutant huntingtin's interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington's disease. Hum. Mol. Genet. 21, 406-420 (2012).
33. Meisinger, C. et al. The mitochondrial morphology protein Mdm10 functions in assembly of the preprotein translocase of the outer membrane. Dev. Cell 7, 61-71 (2004).
34. Altmann, K. & Westermann, B. Role of essential genes in mitochondrial morphogenesis in Saccharomyces cerevisiae. Mol. Biol. Cell 16, 5410-5417 (2005).
35. Milnerwood, A.J. & Raymond, L.A. Early synaptic pathophysiology in neurodegeneration: insights from Huntington's disease. Trends Neurosci. 33, 513-523 (2010).
36. Johri, A. & Beal, M.F. Antioxidants in Huntington's disease. Biochim. Biophys. Acta 1822, 664-674 (2012).
37. Devi, L., Prabhu, B.M., Galati, D.F., Avadhani, N.G. & Anandatheerthavarada, H.K. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J. Neurosci. 26, 9057-9068 (2006).
38. Li, Q. et al. ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import. Proc. Natl. Acad. Sci. USA 107, 21146-21151 (2010).
39. Liu, J. et al. Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43, 5-17 (2004).
40. Roesch, K., Curran, S.P., Tranebjaerg, L. & Koehler, C.M. Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex. Hum. Mol. Genet. 11, 477-486 (2002).
41. Ahting, U. et al. Neurological phenotype and reduced lifespan in heterozygous Tim23 knockout mice, the first mouse model of defective mitochondrial import. Biochim. Biophys. Acta 1787, 371-376 (2009).
42. Vögtle, F.N. & Meisinger, C. Sensing mitochondrial homeostasis: the protein import machinery takes control. Dev. Cell 23, 234-236 (2012).
43. Shao, J. & Diamond, M.I. Polyglutamine diseases: emerging concepts in pathogenesis and therapy. Hum. Mol. Genet. 16, R115-R123 (2007).
44. Zoghbi, H.Y. & Orr, H.T. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23, 217-247 (2000).
45. Cui, L. et al. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127, 59-69 (2006).
46. Weydt, P. et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab. 4, 349-362 (2006).
47. Humphries, A.D. et al. Dissection of the mitochondrial import and assembly pathway for human Tom40. J. Biol. Chem. 280, 11535-11543 (2005).
48. Trettel, F. et al. Dominant phenotypes produced by the HD mutation in STHdhQ111 striatal cells. Hum. Mol. Genet. 9, 2799-2809 (2000).
49. Ehrlich, M.E. et al. ST14A cells have properties of a medium-size spiny neuron. Exp. Neurol. 167, 215-226 (2001).
50. Kristian, T. Isolation of mitochondria from the CNS. Curr. Protoc. Neurosci. 7, 7.22 (2010).
51. 2+-induced permeability transition in energized liver mitochondria discriminates between inhibitor mechanisms. J. Biol. Chem. 283, 665-676 (2008).
52. Yano, M., Hoogenraad, N., Terada, K. & Mori, M. Identification and functional analysis of human Tom22 for protein import into mitochondria. Mol. Cell. Biol. 20, 7205-7213 (2000).
53. Terada, K. et al. Participation of the import receptor Tom20 in protein import into mammalian mitochondria: analyses in vitro and in cultured cells. FEBS Lett. 403, 309-312 (1997).
54. Kim, A.H. et al. A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 136, 322-336 (2009).