JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M209356200 on October 21, 2002

J. Biol. Chem., Vol. 277, Issue 52, 50966-50972, December 27, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/52/50966    most recent
M209356200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takeuchi, H.
Right arrow Articles by Sobue, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takeuchi, H.
Right arrow Articles by Sobue, G.

Mitochondrial Localization of Mutant Superoxide Dismutase 1 Triggers Caspase-dependent Cell Death in a Cellular Model of Familial Amyotrophic Lateral Sclerosis*

Hideyuki Takeuchi, Yasushi Kobayashi, Shinsuke Ishigaki, Manabu Doyu, and Gen SobueDagger

From the Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

The mutations in superoxide dismutase 1 (SOD1) cause ~20% of familial amyotrophic lateral sclerosis cases. A toxic gain of function has been considered to be the cause of the disease, but its molecular mechanism remains uncertain. To determine whether the subcellular localization of mutant SOD1 is crucial to mutant SOD1-mediated cell death, we produced neuronal cell models with accumulation of SOD1 in each subcellular fraction/organelle, such as the cytosol, nucleus, endoplasmic reticulum, and mitochondria. We showed that the localization of mutant SOD1 in the mitochondria triggered the release of mitochondrial cytochrome c followed by the activation of caspase cascade and induced neuronal cell death without cytoplasmic mutant SOD1 aggregate formation. Nuclear and endoplasmic reticulum localization of mutant SOD1 did not induce cell death. These results suggest that the localization of mutant SOD1 in the mitochondria is critical in the pathogenesis of mutant SOD1-associated familial amyotrophic lateral sclerosis.

* This work was supported by grants from the Ministry of Health, Labor and Welfare of Japan and a Center of Excellence grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed. Tel.: 81-52-744-2385; Fax: 81-52-744-2384; E-mail: sobueg@med.nagoya-u.ac.jp.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. Son, S. C. Leary, N. Romain, F. Pierrel, D. R. Winge, R. G. Haller, and J. L. Elliott
Isolated Cytochrome c Oxidase Deficiency in G93A SOD1 Mice Overexpressing CCS Protein
J. Biol. Chem., May 2, 2008; 283(18): 12267 - 12275.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Wang, H. Takeuchi, Y. Sonobe, S. Jin, T. Mizuno, S. Miyakawa, M. Fujiwara, Y. Nakamura, T. Kato, H. Muramatsu, et al.
Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population
PNAS, March 11, 2008; 105(10): 3915 - 3920.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. Sau, S. De Biasi, L. Vitellaro-Zuccarello, P. Riso, S. Guarnieri, M. Porrini, S. Simeoni, V. Crippa, E. Onesto, I. Palazzolo, et al.
Mutation of SOD1 in ALS: a gain of a loss of function
Hum. Mol. Genet., July 1, 2007; 16(13): 1604 - 1618.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
R. Gomel, C. Xiang, S. Finniss, H. K. Lee, W. Lu, H. Okhrimenko, and C. Brodie
The Localization of Protein Kinase C{delta} in Different Subcellular Sites Affects Its Proapoptotic and Antiapoptotic Functions and the Activation of Distinct Downstream Signaling Pathways
Mol. Cancer Res., June 1, 2007; 5(6): 627 - 639.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
F. TANAKA, J.-I. NIWA, S. ISHIGAKI, M. KATSUNO, M. WAZA, M. YAMAMOTO, M. DOYU, and G. SOBUE
Gene Expression Profiling toward Understanding of ALS Pathogenesis
Ann. N.Y. Acad. Sci., November 1, 2006; 1086(1): 1 - 10.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. D. Atkin, M. A. Farg, B. J. Turner, D. Tomas, J. A. Lysaght, J. Nunan, A. Rembach, P. Nagley, P. M. Beart, S. S. Cheema, et al.
Induction of the Unfolded Protein Response in Familial Amyotrophic Lateral Sclerosis and Association of Protein-disulfide Isomerase with Superoxide Dismutase 1
J. Biol. Chem., October 6, 2006; 281(40): 30152 - 30165.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Ferri, M. Cozzolino, C. Crosio, M. Nencini, A. Casciati, E. B. Gralla, G. Rotilio, J. S. Valentine, and M. T. Carri
Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials
PNAS, September 12, 2006; 103(37): 13860 - 13865.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Takeuchi, S. Jin, J. Wang, G. Zhang, J. Kawanokuchi, R. Kuno, Y. Sonobe, T. Mizuno, and A. Suzumura
Tumor Necrosis Factor-{alpha} Induces Neurotoxicity via Glutamate Release from Hemichannels of Activated Microglia in an Autocrine Manner
J. Biol. Chem., July 28, 2006; 281(30): 21362 - 21368.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
T. J. Lukas, W. W. Luo, H. Mao, N. Cole, and T. Siddique
Informatics-assisted Protein Profiling in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
Mol. Cell. Proteomics, July 1, 2006; 5(7): 1233 - 1244.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. M. Schonhoff, M. Matsuoka, H. Tummala, M. A. Johnson, A. G. Estevéz, R. Wu, A.és Kamaid, K. C. Ricart, Y. Hashimoto, B. Gaston, et al.
S-nitrosothiol depletion in amyotrophic lateral sclerosis
PNAS, February 14, 2006; 103(7): 2404 - 2409.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
P J Shaw
Molecular and cellular pathways of neurodegeneration in motor neurone disease
J. Neurol. Neurosurg. Psychiatry, August 1, 2005; 76(8): 1046 - 1057.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
S. Antonyuk, J. S. Elam, M. A. Hough, R. W. Strange, P. A. Doucette, J. A. Rodriguez, L. J. Hayward, J. S. Valentine, P. J. Hart, and S. S. Hasnain
Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg
Protein Sci., May 1, 2005; 14(5): 1201 - 1213.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
F. Di Lisa and P. Bernardi
Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition
Cardiovasc Res, May 1, 2005; 66(2): 222 - 232.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Takeuchi, T. Mizuno, G. Zhang, J. Wang, J. Kawanokuchi, R. Kuno, and A. Suzumura
Neuritic Beading Induced by Activated Microglia Is an Early Feature of Neuronal Dysfunction Toward Neuronal Death by Inhibition of Mitochondrial Respiration and Axonal Transport
J. Biol. Chem., March 18, 2005; 280(11): 10444 - 10454.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
I. G. Kirkinezos, S. R. Bacman, D. Hernandez, J. Oca-Cossio, L. J. Arias, M. A. Perez-Pinzon, W. G. Bradley, and C. T. Moraes
Cytochrome c Association with the Inner Mitochondrial Membrane Is Impaired in the CNS of G93A-SOD1 Mice
J. Neurosci., January 5, 2005; 25(1): 164 - 172.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
K. Fukada, F. Zhang, A. Vien, N. R. Cashman, and H. Zhu
Mitochondrial Proteomic Analysis of a Cell Line Model of Familial Amyotrophic Lateral Sclerosis
Mol. Cell. Proteomics, December 1, 2004; 3(12): 1211 - 1223.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.